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Undesirable side effects and multidrug tolerance are the main holdbacks to the treatment of cancer in conventional chemotherapy. Fortunately, targeted drug delivery can improve the enrichment of drugs at the target site and reduce toxicity to normal tissues and cells. A targeted drug delivery system is usually composed of a nanocarrier and a targeting component. The targeting component is called a “ligand”. Aptamers have high target affinity and specificity, which are identified as attractive and promising ligands. Therefore, aptamers have potential application in the development of smart targeting systems. For instance, aptamers are able to efficiently recognize tumor markers such as nucleolin, mucin, and epidermal growth factor receptor (EGFR). Besides, aptamers can also identify glycoproteins on the surface of tumor cells. Thus, the aptamer-mediated targeted drug delivery system has received extensive attention in the application of cancer therapy. This article reviews the application of aptamers as smart ligands for targeted drug delivery in cancer therapy. Special interest is focused on aptamers as smart ligands, aptamer-conjugated nanocarriers, aptamer targeting strategy for tumor microenvironment (TME), and aptamers that are specified to crucial cancer biomarkers for targeted drug delivery.
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1. Introduction
Cancer is one of the top threats to human health. It is estimated that 19 million new cancer cases and 9.9 million cancer deaths occurred worldwide in 2020 [1,2]. Recently, the treatment of cancer is hindered by the complexity and heterogeneity of tumor biology [3,4,5]. In general, most conventional chemotherapeutics will result in nonspecific systemic biodistribution of the drug, inducing cytotoxicity to healthy tissues [6,7]. In addition to poor selectivity, inadequate drug concentration at tumor sites and multidrug resistance generated unsatisfactory therapeutic outcomes. Hence, a targeted drug delivery system is essential to overcome the limitations of current cancer treatment [8,9,10].
Targeted drug delivery systems have advantages over conventional chemotherapy drugs, such as prolonging the circulating half-life of drugs and improving their bioavailability, stability, and tumor accumulation of drugs [11,12,13]. These modifiable physicochemical properties can be used in targeting protocols to ameliorate the biodistribution and target site accumulation of conventional cancer drugs. A targeted drug delivery system usually consists of a nanocarrier and a targeting element [12,14,15]. The targeting element is called a “ligand”. Many ligand molecules, such as bile salts, vitamins, transferrin, saccharides, lectins, antibodies, oligopeptides, and aptamers are currently available for the development of a targeted drug delivery system [16,17,18]. In comparison with conventional small molecule ligands, aptamers have the potential of facile synthesis, simple modification, and exceedingly high specificity in cell-surface aptamer targets, which makes aptamers as an excellent ligand for a targeted drug delivery system [19,20,21].
Aptamers, short RNA or single-stranded DNA, are composed of 20–80 nucleotides, which are considered to be chemical antibodies (Figure 1) [22,23]. Aptamers, acted as pleiotropic ligands, have potential for application in the construction of intelligent targeting systems [24]. The discovery and application of aptamers have been reviewed by previous researchers. There are many reports and studies on aptamer synthesis, aptamer-mediated therapy, and biomedical imaging as a biometric molecule [25,26,27,28]. In recent years, aptamers, acted as targeting agents to modify and bind nanocarriers, have become a hotspot for cancer drug administration and treatment. Some progress has also been made in the research of aptamers that directly bind drugs for tumor targeting, but this review focuses on the application of aptamer-modified nanocarriers as nano-drug delivery systems in cancer therapy. Aptamers are able to efficiently recognize tumor markers such as nucleolin, mucin, and EGFR [28,29,30]. Besides, aptamers can also identify glycoproteins on the surface of tumor cells. Thus, the aptamer-mediated targeted drug delivery system has received extensive attention in the application of cancer therapy [31,32]. This article includes a review of the application of aptamers in targeted cancer therapy, aptamers as smart ligands, aptamer-conjugated nanocarriers, aptamer targeting strategy for tumor microenvironment (TME), and aptamers that are specified to crucial cancer biomarkers for targeted drug delivery are discussed in this work [33,34].
2. Aptamers as Smart Ligands
Aptamers are specialized short segments of single-stranded DNA/RNA that have been of increasing interest to researchers in applications since 1990 [35,36,37,38]. The Gold and Szostak labs first described a nucleic acid molecular recognition element. For the first time, the Gold lab described a process that is now known as systematic evolution of ligands by exponential enrichment (SELEX), which identifies one or several molecular recognition elements (MREs) with high affinity and specificity for the intended target [39]. These MREs were later named aptamers [40,41]. The SELEX process usually starts with a chemically-synthesized random oligonucleotide library of different sequences (Figure 2). A single nucleic acid aptamer consists of a specific sequence that evolved from the SELEX program, flanked by two constant primer regions during polymerase chain reaction (PCR) amplification [42,43]. The targets of selection are first incubated under specific ionic and temperature conditions [44]. Molecules that bound to the target are retained and amplified by PCR, while non-bound molecules are discarded.
An aptamer has many advantages. It can bind to specified targets, such as proteins, small molecules, and cells. It also plays a significant role in the recognition of tumor markers, inflammatory factors, and immune cells [45,46]. Compared with other molecular recognizers, the biggest advantage of aptamers is that they have almost no immunogenicity, so they have a very wide range of targeting recognition and binding spectrum. Aptamers are easy to couple to nanocarriers and hardly increase the size of the composite nanocarriers. Aptamers are relatively easy to prepare and store. In comparison with monoclonal antibodies, aptamers have efficient uptake in the presence of specific cell-surface aptamer targets [47,48]. In addition, the establishment of cell-SELEX technology enables aptamers to be used to construct highly targeted cancer nanocarriers (Figure 3) [49]. Cell-SELEX technology was developed in 2003 and uses whole living cells to select aptamers, that are targeted to the cell surface [50]. Cell-SELEX technology and its derivation methods can screen aptamers that can effectively distinguish cancer cells from normal cells. Therefore, aptamers can be used as smart ligands [51,52,53,54].
3. Aptamer-Conjugated Nanocarrier Delivery
Nano-targeted drug delivery systems typically consist of a nanocarrier and a targeting component. Nanocarriers have become a promising strategy for tumor-targeted drug delivery due to their unique physical and biological properties. Due to their size characteristics, nano-carriers can enter the blood circulation of the human body. While nanocarriers was loaded drugs (small molecule drugs, protein, genes, and other macromolecular drugs), nanocarriers can slow down drug degradation and renal clearance, increase the half-life of drugs in the blood, and improve their efficacy [55,56]. Due to the increased permeability of tumor neovascularization and its weak lymphatic drainage, nanocarriers can be enriched in tumor tissue to achieve the effect of passive cancer targeting. The selection and preparation of nanocarriers should meet the following requirements: good biocompatibility that includes tissue/blood compatibility and non-immunogenicity; certain mechanical strength as well as be easy to process; and the rate of drug release is moderate and stable. Nanocarriers can be divided into two major categories: inorganic and organic nanocarriers [57,58]. Inorganic nanocarriers mainly include mesoporous silica and magnetic nanoparticles. Organic nanocarriers mainly include polysaccharides, liposomes, and DNA tetrahedron nanostructures (DTNs), which have the characteristics of good biocompatibility and high drug loading rate. Combined with aptamers, nano-delivery systems can improve the specific delivery and precise release of cancer drugs (Figure 4). The drug loading system without aptamer modification only has passive targeting, but non-active targeting. Aptamers that are modified on the surface of nanocarriers can be used as biological recognition molecules for the active targeting of tumor cells. The aptamer-functionalized nanocarriers become intelligent drug carriers with significant drug delivery and targeting properties. The combination of aptamers and nanotechnology has enabled the further application of various targeted drug delivery systems in clinical therapy and diagnosis. Aptamers can bind to nanocarriers in covalent or non-covalent methods. Covalent binding is mainly through the aptamer and the group on the surface of the drug carrier. Non-covalent binding has high affinity and electrostatic interactions [59,60,61]. For instance, Lohiya et al. developed a chitosan-coated (pH-responsive), doxorubicin (DOX)-loaded aptamer -MSNs bioconjugate for the active targeting of breast cancer cells overexpressing epidermal growth factor receptor (EGFR/HER2) [59]. Most aptamer-modified nanocarriers adopt a covalent binding, because they have no additional side effects such as cytotoxicity [62]. The application of nanocarriers combined with aptamers in a targeted delivery system for tumor treatment has attracted extensive attention.
3.1. Inorganic Nanocarriers
Inorganic materials have the advantages of nontoxicity, biocompatibility, hydrophilicity, and high stability, and are widely used in the field of drug delivery [63]. The main inorganic nanocarriers include mesoporous silica nanoparticles (MSNs) and magnetic nanoparticles (MNPs), which possess some unique characteristics in drug delivery, including high specific surface area, controllable shape and size, and easy surface modification. Inorganic nanocarriers also have the function of stimulus-responsive drug release [64].
Inorganic nanocarrier-conjugated aptamers are widely used in cancer diagnosis, imaging, and treatment. For instance, DNA aptamer-coupled calcium-phosphosilicate nanoparticles (known as NanoJackets, NJs) are used for the non-invasive detection of prostate and pancreatic tumors [65]. MSNs have attracted much attention in drug delivery due to their high specific surface area, large pore volume, adjustable pore structure, and high surface modifiability [66,67,68]. Similar to other inorganic nanoparticles, MSNs can effectively bind drugs and target drug delivery to the tumor site. As MSNs can protect the encapsulated drug from being recognized by efflux transporters, the drug-carrying MSNs can transport the drug to the cytoplasm after entering the cancer cells, and eventually kill the cancer cells [69]. MSNs can bind the drug EPI and mucin 1 (MUC1) aptamer, demonstrating that MSNs-MUC1-EPI has targeted delivery and a therapeutic effect on MUC1-positive breast cancer cells [70]. The aptamer-MSNs-DOX delivery system is also performed by modifying an aptamer targeting epithelial cell adhesion molecule (EpCAM) to DOX-loaded MSNs. Aptamer-MSN-DOX can be targeted to EpCAM-positive colon cancer cells, improve the efficacy, and reduce toxic side effects [71]. Vivo-Llorca et al. modified MSNs with a MUC1 aptamer to overcome drug resistance for the targeted treatment of triple-negative breast cancer (TNBC) [72]. Aptamer-functionalized MSNs for cancer targeted therapies are listed in Table 1.
MNPs are widely used nanomaterials [81,82], which were first proposed in the 1970s for the clinical targeted treatment of cancer [81,83]. As tumor cells are sensitive to rising temperature, MNPs can release heat through alternating magnetic field stimulation after entering tumor cells, destroying the internal structure of tumor cells to kill cancer cells [84,85,86]. A common strategy is coating poly(lactic-co-glycolic acid) (PLGA) nanoparticles with MNPs. This MNPs system is loaded with a dual drug that is bound by aptamers, which can effectively target the drug to the tumor cells for achieving the targeted therapy effect [87]. Other statements are shown in Table 2.
3.2. Organic Nanocarriers
Natural nanocarriers have higher biocompatibility and biodegradability, greater safety, and physiological stability than inorganic nanocarriers. Organic nanocarriers with different stimulation responses have been further applied and developed in the treatment of cancer [64]. Therefore, it has been extensively and deeply studied. Organic nanocarriers mainly include polysaccharides, liposomes, and synthetic polymer nanocarriers [92,93,94].
Polysaccharides are natural biopolymers that play different roles in microorganisms, plants, and animals [95,96]. Polysaccharides are polymeric carbohydrates that are composed of at least more than 10 monosaccharides bound by glycosidylic bonds. Polysaccharides that are composed of the same monosaccharides are called isopolysaccharides, such as starch, cellulose, and glycogen. Natural polysaccharides are excellent nanocarriers because of their superior properties with availability, biocompatibility, and extraordinary biodegradability [97]. Due to these excellent properties, natural polysaccharides are widely used in the design of nanocarriers and have a wide range of applications in the delivery and protection of biologically active compounds or drugs [98,99]. Chitosan is a representative kind of matrix. In addition, natural polysaccharides can also be used as a targeted therapy through mechanisms such as specific enzymatic hydrolysis, binding to receptors, pH triggering, and mucosal adhesion [100]. For example, the MUC1 aptamer was used to functionalize chitosan-coated human serum albumin nanoparticles to obtain a selective drug carrier for tumors that were overexpressing MUC1. Besides, chitosan combined with aptamer-coated nanoparticles have strong cytotoxicity and can be used as a potential target tumor drug delivery system [101].
Liposomes are widely used in medicine as nanocarrier systems. Liposomes are vesicles with an aqueous volume that is completely enclosed by a phospholipid membrane. Liposomes range in size from 30 nm to a few microns and can be single or multilayered, where each layer is a bilayer [102]. They play a unique role in combatting drug resistance and improving drug stability [103]. Lipid-based systems include liposomes, solid lipid nanoparticles (SLNs), and cationic liposomes (CLPs). Encapsulation or conjugation of liposome nanocarriers can prolong the half-life of antitumor drugs in blood circulation and significantly improve the stability of drugs in vivo. The aptamer AS1411 was coupled to polyethylene glycolpegylated (PEGylated) CLPs and used as a targeting probe ASLP (AS1411-PEG-CLPs). In addition, the novel siRNA delivery system targeting nucleolar proteins by AS1411 is a potential therapeutic strategy for melanoma [104]. Representative aptamer-functionalized liposomal nanocarriers for cancer targeted therapy are shown in Table 3.
Synthetic polymer nanocarriers mainly include semi-synthetic or synthetic polymers PLGA-PEG, N-(2-hydroxypropyl) methylacrylamide (HPMA), polyacrylamide (PAM), and polyetherimide (PEI), which also have the characteristics of biocompatibility, biodegradation and high drug loading. Polymer nanocarriers with different diameters and shapes can be synthesized or self-assembled by some effective methods for the loading and delivery of different anticancer drugs. There are many reports on the synthesis of polymers by aptamer binding. The binding of polyethyleneimine to gold nanoparticles (AuNPs) that were functionalized with aptamer AS1411 and DOX (PEI-g-PEG) is a promising polymer composite strategy. The prepared AS1411-g-DOX-g-PEI-g-PEG@AuNPs nanoparticles have a diameter of 39.9 nm and can stably exist in water and cellular media, which improves the stability of DOX-AuNPs. In the cell experiment, the cancer cell (A549) can be eliminated [110]. Other studies on aptamer functionalization of synthetic polymer nanocarriers for cancer therapies are listed in Table 4.
3.3. DNA Nanostructures as Nanocarriers
DNA nanostructures, which can penetrate cell membranes, are an excellent strategy as nanocarriers. DNA 3D tetrahedron nanostructures have recently generated interest in DNA nanotechnology. DTNs combined with the AS1411 aptamer as capture probes can achieve efficient capture of cancer cells, and this DTNs combined with fluorescent materials can be used for the early diagnosis and clinical treatment of cancer [117]. Gong et al. designed a bimolecular G-tetramer (G4) and adenosine triphosphate (ATP) aptamer as a logical control unit to develop intelligent DNA nano-assembly controlled by YES-AND logical circuits, which has great prospects for intelligent anticancer drug delivery [118]. Specific binding of PD-L1 and Pcsk9 siRNA on well-defined TDNs by DNA hybridization can target the release of immune cells to colon cancer cells and contribute to the treatment of CRC [119]. Other aptamer-targeted cancer therapies that are based on DNA tetrahedral nanocarriers are listed in Table 5.
3.4. Disadvantages and Challenges of Nanocarriers
Despite the unique advantages of nanocarriers in the delivery of active anticancer drugs, only a few studies have emerged. For instance, liposomes can improve drug stability in vivo, but they are not stable enough in individual storage, their encapsulation rate is low, and their drug load is small. PEI nanocarriers have made limited progress in clinical practice due to their toxicity and in vivo instability. In inorganic nanocarriers, how to improve the biodegradability of MSNs is an urgent problem to be solved. The preparation process of MNPs is complicated and the particle morphology and structure are not easy to control. In addition, they are vulnerable to oxidation and acid and alkali corrosion during storage. In summary, how to simplify the preparation of nanocarriers, reduce the difficulty of storage, and improve the drug loading rate and biodegradability is still a topic of research in the field of nano-drug delivery systems.
4. Aptamer Targeting Strategy for Tumor Microenvironment
Compared with normal tissues, the internal tissues of tumors have a very complex and highly heterogeneous microenvironment due to abnormal metabolism and proliferation at the tumor site [131,132]. Its internal characteristics mainly include abnormal expression of adenosine triphosphate (ATP), glutathione (GSH), and reactive oxygen species (ROS).
During the course of cancer development and progression, ATP, a major metabolite adenosine, and possibly other nucleotides are actively secreted, passively released, or generated in the extracellular environment and play key roles as extracellular messengers. In healthy tissues, the extracellular accumulation of nucleotides and nucleosides is almost negligible. In contrast, ATP and adenosine accumulate at high levels at sites of inflammation and tumors. Thus, the overexpression of ATP can be used as a target that is recognized by aptamers for tumor-targeted drug delivery [133]. For instance, using ATP and MUC1 aptamers that were immobilized on the surface of MSNs. The ATP aptamers leave the surface of MSNs and start drug release after cancer cells have mediated endocytosis through MUC1 receptors [134]. In addition, the AS1411-ATP aptamer chimera can be used as a novel approach to selectively deliver DOX to cancer cells, a strategy that has the potential to increase DOX efficacy and reduce toxicity to normal cells [135].
With respect to cancer, GSH has dual effects in its progression. Excessive reduced glutathione promoted tumor progression, and elevated levels correlate with increased metastasis [136,137]. Thus, glutathione levels can be used to detect cancer progression and can also be used as a delivery target for antitumor drug delivery systems [138,139]. Experiments on human breast cancer cells in vitro showed that glutathione binding RNA aptamer is expected to develop into an effective anticancer and chemotherapy drug [140]. DOX was inserted into an ATP aptamer DNA scaffold and then modified to obtain poly(oxyethylene)-imide (POEI)/DOX/ATP aptamer NPs targeting 3CDIT. The dual responsive release of GSH and ATP made DOX enriched in tumor cells, thus ensuring the effectiveness and safety of glioma chemotherapy [141]. The use of an MNP binding aptamer (MNP/SGc8-SP) to detect glutathione content and expression is a promising and efficient targeted tumor delivery system [142].
ROS are a series of molecules that are produced by intracellular oxidative metabolism, including singlet oxygen (primary excited state), superoxide anion (single-electron state), hydroxyl radical (three-electron state), and hydrogen peroxide (two-electron state) [143,144]. In the TME, a low levels of ROS play important roles in signaling, cell proliferation, and revascularization. The gradual elevation of ROS can also promote tumor cell proliferation and metastasis [145,146]. Over-expressed ROS can damage the DNA of cancer cells, leading to apoptosis and tumor necrosis to a certain extent. Tumor cells have fast growth rate, strong reproductive ability and strong metabolic capacity. Besides, their demand for nutrients is higher than that of normal cells. Therefore, ROS are closely related to various stages of tumors, and the expression level of ROS can be used as a target for aptamer nano-drug delivery systems. For example, phorbol-12-myristate-13-acetate (PMA) was released in HL-60 cancer cells to induce the production of ROS, after the aptamer on MSNs specifically recognized and targeted binding to HL-60 cancer cells. ROS effectively induced apoptosis in HL-60 cells [147]. A priming strategy was developed to selectively kill tumor cells by combining singlet oxygen quenching MnO2 with a tumor cell-targeting aptamer. Aptamers on the surface of nanoparticles can recognize proteins on the surface of tumor cells and specifically bind to the induced singlet oxygen production "on-off" switch, which produce high concentrations of ROS at the tumor site to kill the target tumor cells [148].
5. Aptamers Specific to Important Crucial Cancer Biomarkers for Targeted Drug Delivery
Cancer biomarkers are molecules that indicate the abnormal cancer status and play important roles in many biological processes, including cell proliferation, cell migration and cell–cell interactions [149,150,151,152,153]. Most cancer biomarkers are proteins [154]. Aptamers with high specificity and affinity for certain tumor surface proteins can be selected from the existing aptamers or DNA/RNA libraries as molecular recognizers to enhance the targeting of nano-drug vectors [155,156,157]. These biomarkers can serve as reliable targets for aptamer drug delivery systems because of the high binding capacity and specificity of aptamers. Specifically, numerous aptamers target cancer-specific signature markers such as human cluster of differentiation antigen 133 (CD133), CD44, and EpCAM. This section lists several representative tumor biomarkers and the corresponding research on aptamer targeting strategies, as well as some other novel research applications (Figure 5).
CD133, a glycoprotein with five transmembrane structural domains that was identified from mouse neuroepithelial stem cells and human hematopoietic stem cells, is a widely recognized tumor stem cell marker [158,159,160,161,162,163,164,165,166]. CD133-coordinated aptamers can be used for the detection of some tumors and targeted delivery of chemotherapeutic agents. The aptamer targeting CD133 was hybridized with partial complementary paired RNA (ssRNA) and modified on the surface of quantum dots (QDs) and AuNPs to construct aptamer nanosensors [167]. PLGA-PEG NPs coupled with a paclitaxel-loaded CD133 aptamer (N-Pac-CD133) were designed to eliminate lung cancer stem cells, and the results showed that N-Pac-CD133 had significantly enhanced targeting and efficacy against lung cancer stem cells [168]. Zahiri et al. prepared a dendritic MSNs-based (DMSN-based), pH-responsive nanoparticle that was functionalized with a CD133 aptamer that was released due to pH changes after endocytosis by tumor cells [169]. A propranolol aptamer-loaded CD133 polylactic acid-glycolic acid copolymer nanoparticle (PPNCD133) was designed for the treatment of infantile hemangioma and showed promising effects on hemangioma [170]. A PEGylated acetylated carboxymethyl cellulose conjugate of SN38 (7-ethyl-10-hydroxycamptothecin) was developed to covalently bind to an aptamer targeting CD133. This nanoplatform was used to specifically deliver SN38 to colorectal cancer cells. Ligand-modified PEG-AcCMC-SN38 nanoparticles with a size of less than 200 nm showed enhanced cellular uptake in CD133-positive HT29 cell lines. In conclusion, the prepared Apt-PEGAcCMC-SN38 can be considered as a promising targeted delivery system for SN38 prodrugs [171].
CD44 is a transmembrane molecule with multiple isoforms that overexpresses in many tumors and promotes tumor formation by interacting with the TME [172,173,174,175,176,177]. CD44 has been implicated in malignant processes including cell motility, tumor growth, and angiogenesis. Alshaer et al. successfully conjugated a 2′-F-pyrimidine-containing RNA aptamer (Apt1) targeting CD44 to the surface of PEGylated liposomes using the thiol-maleimide click reaction. Flow cytometry and confocal imaging were used to detect the uptake of Apt1-Lip by cancer cells. The results showed that the Apt1-Lip was prepared in this article and has higher sensitivity, selectivity and potentiality as a specific drug delivery system [178]. Kim et al. conducted an attractive study of drug-loaded liposomes linked with two DNA aptamers that targeted the surface marker transmembrane glycoprotein MUC1 on breast cancer cells and the surface glycoprotein CD44 antigen on breast cancer stem cells (CSCs). Dual-aptamer-conjugated liposomes (referred to as dual-aptamersomes) were prepared to encapsulate DOX and tested for doxorubicin delivery to 3D cultured breast cancer cells and CSCs. The cytotoxicity of dual-Apt-DOX on CSCs and cancer cells was significantly higher than that of liposomes lacking aptamers [179]. Darabi et al. designed SLNs containing DOX that was decorated with anti-EGFR/CD44 double RNA aptamers. The results indicated that SLNs/DOX/Dexa/CD44/EGFR was a promising new enhanced anticancer delivery system that warranted further clinical trials [109].
An epithelial cell adhesion molecule (EpCAM) is an antigen that is expressed in cancer stem cells and epithelial cells [180]. It was first discovered in 1979 on colon cancer cells [181]. EpCAM is expressed frequently and at high levels in various cancers but at low levels in normal cells [182]. These characteristics make it a biomarker and a therapeutic target for cancer cells [183]. For instance, Zhao et al. developed a cationic liposome-based nanoparticle that was loaded with miR-139-5p (miR-139-5p-HSPC/DOTAP/Chol/DSPE-PEG2000-COOH nanoparticles, MNPs) and surface that was decorated with EpCAM Apt (miR-139-5p-EpCAM Apt-HSPC/DOTAP/Chol/DSPE-PEG2000-COOH NPs, MANPs) for the CRC targeted treatment [184]. In addition, an EpCAM RNA aptamer-conjugated PEGylated liposomal DOX (ER-lip) was also designed for targeted cancer therapy, which demonstrated that ER-lip could promote the survival of animal models and reduce the tumor growth rate. This ER-lip can be used as an ideal drug delivery system for the treatment of tumors with high expression of EpCAM [185]. In the study by Khezrian et al., the surface-active hydrophilic side of functional amphiphilic Janus nanoparticles (JNPs) was functionalized with aptamers against EpCAM to deliver DOX to HT29 cells of metastatic colorectal cancer [186].
6. Conclusions
Due to the advantages of DNA/RNA aptamers in biological recognition and binding, they are widely used in intelligent targeted drug delivery, and have become a research hotspot of biological targeting materials. The aptamer derivatives that have been designed and synthesized can specifically recognize tumor markers such as tumor surface glycoproteins. Furthermore, aptamer derivatives play a unique role in the detection of cancer stem cells and the targeted delivery of chemotherapy drugs.
However, the limitations of aptamers in clinical application still exist. To date, the stability and security of the systemic administration of aptamers have not been approved by regulatory agencies such as the FDA. The FDA has only registered one aptamer drug for local administration at the site of action. Furthermore, the affinity and selectivity of aptamers are key factors for targeted drug delivery. Nucleic acid aptamers that are bound or immobilized on nanostructures may change their three-dimensional conformation, leading to changes in affinity and selectivity. In addition, cancer surface biomarkers are highly inconsistent and may be differentially expressed between individuals. Therefore, there is no universal law for the affinity and selectivity of aptamers in cancer therapy, which cannot be determined by a single study expanding into a field. With the progress of technology, these problems will be properly solved.
Conceptualization, Z.W. and J.W.; methodology, R.W. and Y.Z.; validation, J.W. and Z.C.; formal analysis, J.W. and Z.C.; investigation, J.W. and Z.C.; data curation, J.W. and Z.C.; writing—original draft, Z.W.; writing—review and editing, R.W. and Y.Z.; supervision, J.W. and Z.C.; funding acquisition, J.W. and Z.C. All authors have read and agreed to the published version of the manuscript.
Not applicable.
Not applicable.
Not applicable.
The authors declare no conflict of interest.
| 5-FU | 5-fluorouracil |
| ALCL | anaplastic large cell lymphoma |
| Apt | aptamer |
| ATP | adenosine triphosphate |
| AuNPs | gold nanoparticles |
| CD133 | differentiation antigen 133 |
| CLPs | cationic liposomes |
| CRC | colorectal cancer |
| CSCs | cancer stem cells |
| CTCs | circulating tumor cells |
| DOX | doxorubicin |
| DTNs | DNA tetrahedron nanostructures |
| DTX | docetaxel |
| EGFR | epidermal growth factor receptor |
| EpCAM | epithelial cell adhesion molecule |
| EPI | epirubicin |
| FITC | fluorescein isothiocyanate |
| G4 | G-tetramer |
| GSH | glutathione |
| HCC | hepatocellular carcinoma |
| HPMA | N-(2-hydroxypropyl) methylacrylamide |
| JNPs | janus nanoparticles |
| MNPs | magnetic nanoparticles |
| MREs | molecular recognition elements |
| MSNs | mesoporous silica nanoparticles |
| MUC1 | mucin 1 |
| MUC16 | mucin16 |
| NPs | nanoparticles |
| OXA | oxaliplatin |
| PA | pyrochlorophyll A |
| PAM | polyacrylamide |
| PCR | polymerase chain reaction |
| PEG | polyethylene glycolpegylated |
| PEI | polyetherimide |
| PLGA | poly(lactic-co-glycolic acid) |
| PMA | phorbol-12-myristate-13-acetate |
| PTX | paclitaxel |
| QDs | quantum dots |
| ROS | reactive oxygen species |
| SELEX | exponential enrichment |
| siBraf | anti-BRAF siRNA |
| SLNs | solid lipid nanoparticles |
| ssRNA | partial complementary paired RNA |
| TFO | triplex forming oligonucleotides |
| TME | tumor microenvironment |
| TNBC | triple-negative breast cancer |
| TSIIA | tanshinone II-A |
| VEGF | vascular endothelial growth factor |
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Aptamer-functionalized MSNs for cancer targeted therapies.
| Aptamers | Payloads | Cancers | Reference |
|---|---|---|---|
| MUC1 | Epirubicin (EPI) | Breast cancer | [ |
| EpCAM | DOX | Colon cancer | [ |
| MUC1 | Navitoclax | TNBC | [ |
| MUC-1 | Safranin O | Breast cancer | [ |
| EpCAM | DM1 | Colorectal cancer (CRC) | [ |
| HB-5 | DOX | Breast cancer | [ |
| Sgc-8 | DOX | Human acute T-lymphocyte leukemia | [ |
| AS1411 | DOX | MCF7 cells | [ |
| EpCAM | DOX | Human HT-29 tumors | [ |
| EpCAM | miR-328 | SW480 cells | [ |
| NCL-aptamer | DOX | Breast cancer | [ |
Aptamer-functionalized MNPs for cancer targeted therapies.
| Aptamers | Payloads | Targets | Reference |
|---|---|---|---|
| AS1411 | Curcumin and gemcitabine | Pancreatic cancer | [ |
| AS14 and AS42 | Aptamer-modified FeAG nanoparticles | Ehrlich carcinoma cells | [ |
| Sgc-8 | DOX | Lung adenocarcinoma cells (A549) | [ |
| Mucin16 (MUC16) | Erlotinib | Ovarian cancer cells | [ |
| Vascular endothelial growth factor (VEGF) DNA | VEGF DNA aptamer | Ovarian cancer cells | [ |
Aptamer-functionalized liposome nanocarriers for tumor targeted therapies.
| Aptamers | Nanocarriers | Payloads | Cancers | References |
|---|---|---|---|---|
| AS1411 | PEGylated CLPs | Anti-BRAF siRNA (siBraf) | Melanomas | [ |
| AS1411 | PEGylated SLNs | Docetaxel (DTX) | CRC | [ |
| A15 | PEGylated SLNs | Oxaliplatin (OXA) | Hepatocellular carcinoma (HCC) | [ |
| AS1411 | PEGylated liposome | Paclitaxel (PTX) | Renal carcinoma | [ |
| A15 | CLPs | PTX and Survivin siRNA | Brain glioma | [ |
| anti-CD44 and EGFR aptamers | SLNs | DOX | Breast cancer | [ |
Aptamer-functionalized synthesis polymer nanocarriers for cancer therapies.
| Aptamers | Nanocarriers | Payloads | Cancers | References |
|---|---|---|---|---|
| MUC1 | PLA-PEG | DOX | Lung cancer | [ |
| EpCAM | Poly(amino acid)s NPs | Tanshinone II-A (TSIIA) | CRC | [ |
| AS1411 | PA-Apt-CHO-PEG | PA | Breast cancer | [ |
| CD30 | PEG-PLGA | DOX | anaplastic large cell lymphoma (ALCL) | [ |
| A10 | PLGA | Triplex forming oligonucleotides (TFO) | Prostate cancer | [ |
| AS1411 | PEI | 5-fluorouracil (5-FU) | Gastric cancer | [ |
Aptamer-functionalized DNA tetrahedron nanocarriers for cancer therapies.
| Aptamer | Payloads | Cancers | References |
|---|---|---|---|
| Aptamer cluster | DOX | Breast cancer | [ |
| AS1411 | DOX | HeLa and 4T1 cells | [ |
| AS1411 | Cy3 and Cy5 | Breast cancer | [ |
| anti-HER2 | Maytansine | HER2-positive cancer | [ |
| anti-MUC1 | DOX | Breast cancer | [ |
| Gint4.T | DOX | Glioma | [ |
| Pegaptanib | Pegaptanib | Oral cancer cell | [ |
| AS1411 | 5-FU | Bbreast cancer | [ |
| MUC1 and AS1411 | DOX | Breast cancer | [ |
| SL2B | DOX | CRC | [ |
| MUC1 | DOX | Breast cancer | [ |
References
1. Sung, H.; Ferlay, J.; Siegel, R.L.; Laversanne, M.; Soerjomataram, I.; Jemal, A.; Bray, F. Global cancer statistics 2020: Globocan estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin.; 2021; 71, pp. 209-249. [DOI: https://dx.doi.org/10.3322/caac.21660]
2. Xie, Y.; Shi, L.; He, X.; Luo, Y. Gastrointestinal cancers in China, the USA, and Europe. Gastroenterol. Rep.; 2021; 9, pp. 91-104. [DOI: https://dx.doi.org/10.1093/gastro/goab010]
3. Fong, E.L.S.; Harrington, D.A.; Farach-Carson, M.C.; Yu, H. Heralding a new paradigm in 3D tumor modeling. Biomaterials; 2016; 108, pp. 197-213. [DOI: https://dx.doi.org/10.1016/j.biomaterials.2016.08.052]
4. Loponte, S.; Lovisa, S.; Deem, A.K.; Carugo, A.; Viale, A. The many facets of tumor heterogeneity: Is metabolism lagging behind?. Cancers; 2019; 11, 1574. [DOI: https://dx.doi.org/10.3390/cancers11101574]
5. Valtorta, S.; Salvatore, D.; Rainone, P.; Belloli, S.; Bertoli, G.; Moresco, R.M. Molecular and cellular complexity of glioma. Focus on tumour microenvironment and the use of molecular and imaging biomarkers to overcome treatment resistance. Int. J. Mol. Sci.; 2020; 21, 5631. [DOI: https://dx.doi.org/10.3390/ijms21165631]
6. Qiao, J.; Liu, Z.; Fu, Y.-X. Adapting conventional cancer treatment for immunotherapy. J. Mol. Med.; 2016; 94, pp. 489-495. [DOI: https://dx.doi.org/10.1007/s00109-016-1393-4]
7. Kilgallen, A.B.; Stibler, U.; Printezi, M.I.; Putker, M.; Punt, C.J.A.; Sluijter, J.P.G.; May, A.M.; van Laake, L.W. Comparing conventional chemotherapy to chronomodulated chemotherapy for cancer treatment: Protocol for a systematic review. JMIR Res. Protoc.; 2020; 9, e18023. [DOI: https://dx.doi.org/10.2196/18023]
8. Mohanty, C.; Das, M.; Kanwar, J.R.; Sahoo, S.K. Receptor mediated tumor targeting: An emerging approach for cancer therapy. Curr. Drug Deliv.; 2011; 8, pp. 45-58. [DOI: https://dx.doi.org/10.2174/156720111793663606]
9. Kleinstreuer, C.; Feng, Y.; Childress, E. Drug-targeting methodologies with applications: A review. World J. Clin. Cases; 2014; 2, pp. 742-756. [DOI: https://dx.doi.org/10.12998/wjcc.v2.i12.742]
10. Yu, H.; Yang, Z.; Li, F.; Xu, L.; Sun, Y. Cell-mediated targeting drugs delivery systems. Drug Deliv.; 2020; 27, pp. 1425-1437. [DOI: https://dx.doi.org/10.1080/10717544.2020.1831103]
11. Su, Y.; Xie, Z.; Kim, G.B.; Dong, C.; Yang, J. Design strategies and applications of circulating cell-mediated drug delivery systems. ACS Biomater. Sci. Eng.; 2015; 1, pp. 201-217. [DOI: https://dx.doi.org/10.1021/ab500179h]
12. Alotaibi, B.S.; Buabeid, M.; Ibrahim, N.A.; Kharaba, Z.J.; Ijaz, M.; Noreen, S.; Murtaza, G. Potential of nanocarrier-based drug delivery systems for brain targeting: A current review of literature. Int. J. Nanomed.; 2021; 16, pp. 7517-7533. [DOI: https://dx.doi.org/10.2147/IJN.S333657]
13. Prabahar, K.; Alanazi, Z.; Qushawy, M. Targeted drug delivery system: Advantages, carriers and strategies. Indian J. Pharm. Educ.; 2021; 55, pp. 346-353. [DOI: https://dx.doi.org/10.5530/ijper.55.2.72]
14. Ganta, S.; Devalapally, H.; Shahiwala, A.; Amiji, M. A review of stimuli-responsive nanocarriers for drug and gene delivery. J. Control. Release; 2008; 126, pp. 187-204. [DOI: https://dx.doi.org/10.1016/j.jconrel.2007.12.017]
15. Carbone, E.J.; Rajpura, K.; Allen, B.N.; Cheng, E.; Ulery, B.D.; Lo, K.W.H. Osteotropic nanoscale drug delivery systems based on small molecule bone-targeting moieties. Nanomedicine; 2017; 13, pp. 37-47. [DOI: https://dx.doi.org/10.1016/j.nano.2016.08.015]
16. Das, M.; Mohanty, C.; Sahoo, S.K. Ligand-based targeted therapy for cancer tissue. Expert Opin. Drug Deliv.; 2009; 6, pp. 285-304. [DOI: https://dx.doi.org/10.1517/17425240902780166]
17. Farooqi, A.A.; Shu, C.-W.; Huang, H.-W.; Wang, H.-R.; Chang, Y.-T.; Fayyaz, S.; Yuan, S.-S.F.; Tang, J.-Y.; Chang, H.-W. Trail, Wnt, sonic hedgehog, Tgfβ, and miRNA signalings are potential targets for oral cancer therapy. Int. J. Mol. Sci.; 2017; 18, 1523. [DOI: https://dx.doi.org/10.3390/ijms18071523]
18. Gierlich, P.; Mata, A.I.; Donohoe, C.; Brito, R.M.M.; Senge, M.O.; Gomes-da-Silva, L.C. Ligand-targeted delivery of photosensitizers for cancer treatment. Molecules; 2020; 25, 5317. [DOI: https://dx.doi.org/10.3390/molecules25225317]
19. Dua, P.; Kim, S.; Lee, D.-K. Patents on SELEX and therapeutic aptamers. Recent Pat. DNA Gene Seq.; 2008; 2, pp. 172-186. [DOI: https://dx.doi.org/10.2174/187221508786241710]
20. Xuan, W.; Peng, Y.; Deng, Z.; Peng, T.; Kuai, H.; Li, Y.; He, J.; Jin, C.; Liu, Y.; Wang, R. et al. A basic insight into aptamer-drug conjugates (ApDCs). Biomaterials; 2018; 182, pp. 216-226. [DOI: https://dx.doi.org/10.1016/j.biomaterials.2018.08.021]
21. Liu, M.; Zaman, K.; Fortenberry, Y.M. Overview of the therapeutic potential of aptamers targeting coagulation factors. Int. J. Mol. Sci.; 2021; 22, 3897. [DOI: https://dx.doi.org/10.3390/ijms22083897]
22. Hong, K.L.; Sooter, L.J. Single-stranded DNA aptamers against pathogens and toxins: Identification and biosensing applications. Biomed. Res. Int.; 2015; 2015, 419318. [DOI: https://dx.doi.org/10.1155/2015/419318]
23. Kadioglu, O.; Malczyk, A.H.; Greten, H.J.; Efferth, T. Aptamers as a novel tool for diagnostics and therapy. Investig. New Drugs; 2015; 33, pp. 513-520. [DOI: https://dx.doi.org/10.1007/s10637-015-0213-y]
24. Mastronardi, E.; Foster, A.; Zhang, X.; DeRosa, M.C. Smart materials based on DNA aptamers: Taking aptasensing to the next level. Sensors; 2014; 14, pp. 3156-3171. [DOI: https://dx.doi.org/10.3390/s140203156]
25. Zou, X.-M.; Zhou, J.-W.; Song, S.-H.; Chen, G.-H. Screening of oligonucleotide aptamers and application in detection of pesticide and veterinary drug residues. Chin. J. Anal. Chem.; 2019; 47, pp. 488-499. [DOI: https://dx.doi.org/10.1016/S1872-2040(19)61153-9]
26. Zhao, L.-P.; Yang, G.; Zhang, X.-M.; Qu, F. Development of apatmer screening against proteins and its applications. Chin. J. Anal. Chem.; 2020; 48, pp. 560-572. [DOI: https://dx.doi.org/10.1016/S1872-2040(20)60012-3]
27. Xiao, X.; Li, H.; Zhao, L.; Zhang, Y.; Liu, Z. Oligonucleotide aptamers: Recent advances in their screening, molecular conformation and therapeutic applications. Biomed. Pharmacother.; 2021; 143, 112232. [DOI: https://dx.doi.org/10.1016/j.biopha.2021.112232]
28. Wu, X.; Chen, J.; Wu, M.; Zhao, J.X. Aptamers: Active targeting ligands for cancer diagnosis and therapy. Theranostics; 2015; 5, pp. 322-344. [DOI: https://dx.doi.org/10.7150/thno.10257]
29. Shieh, Y.-A.; Yang, S.-J.; Wei, M.-F.; Shieh, M.-J. Aptamer-based tumor-targeted drug delivery for photodynamic therapy. ACS Nano; 2010; 4, pp. 1433-1442. [DOI: https://dx.doi.org/10.1021/nn901374b]
30. Zhu, L.; Yang, J.; Ma, Y.; Zhu, X.; Zhang, C. Aptamers entirely built from therapeutic nucleoside analogues for targeted cancer therapy. J. Am. Chem. Soc.; 2022; 144, pp. 1493-1497. [DOI: https://dx.doi.org/10.1021/jacs.1c09574]
31. Mokhtarzadeh, A.; Tabarzad, M.; Ranjbari, J.; de la Guardia, M.; Hejazi, M.; Ramezani, M. Aptamers as smart ligands for nano-carriers targeting. Trends Anal. Chem.; 2016; 82, pp. 316-327. [DOI: https://dx.doi.org/10.1016/j.trac.2016.06.018]
32. Li, X.; Zhao, Q.; Qiu, L. Smart ligand: Aptamer-mediated targeted delivery of chemotherapeutic drugs and sirna for cancer therapy. J. Control. Release; 2013; 171, pp. 152-162. [DOI: https://dx.doi.org/10.1016/j.jconrel.2013.06.006]
33. Liu, J.; You, M.; Pu, Y.; Liu, H.; Ye, M.; Tan, W. Recent developments in protein and cell-targeted aptamer selection and applications. Curr. Med. Chem.; 2011; 18, pp. 4117-4125. [DOI: https://dx.doi.org/10.2174/092986711797189619]
34. Guan, B.; Zhang, X. Aptamers as versatile ligands for biomedical and pharmaceutical applications. Int. J. Nanomed.; 2020; 15, pp. 1059-1071. [DOI: https://dx.doi.org/10.2147/IJN.S237544]
35. Zhuo, Z.; Yu, Y.; Wang, M.; Li, J.; Zhang, Z.; Liu, J.; Wu, X.; Lu, A.; Zhang, G.; Zhang, B. Recent advances in SELEX technology and aptamer applications in biomedicine. Int. J. Mol. Sci.; 2017; 18, 2142. [DOI: https://dx.doi.org/10.3390/ijms18102142]
36. Fu, Z.; Xiang, J. Aptamers, the nucleic acid antibodies, in cancer therapy. Int. J. Mol. Sci.; 2020; 21, 2793. [DOI: https://dx.doi.org/10.3390/ijms21082793]
37. Keefe, A.D.; Pai, S.; Ellington, A. Aptamers as therapeutics. Nat. Rev. Drug Discov.; 2010; 9, pp. 537-550. [DOI: https://dx.doi.org/10.1038/nrd3141]
38. Ahmadyousefi, Y.; Malih, S.; Mirzaee, Y.; Saidijam, M. Nucleic acid aptamers in diagnosis of colorectal cancer. Biochimie; 2019; 156, pp. 1-11. [DOI: https://dx.doi.org/10.1016/j.biochi.2018.09.009]
39. Tuerk, C.; Gold, L. Systematic evolution of ligands by exponential enrichment: RNA ligands to bacteriophage T4 DNA polymerase. Science; 1990; 249, pp. 505-510. [DOI: https://dx.doi.org/10.1126/science.2200121]
40. Nakamura, Y.; Endo, K.; Adachi, H.; Ishiguro, A. RNA aptamers to translational components. Prog. Mol. Biol. Transl. Sci.; 2009; 90, pp. 369-395. [DOI: https://dx.doi.org/10.1016/S1877-1173(09)90010-2]
41. Saito, S. Selex-based DNA aptamer selection: A perspective from the advancement of separation techniques. Anal. Sci.; 2021; 37, pp. 17-26. [DOI: https://dx.doi.org/10.2116/analsci.20SAR18]
42. Gopinath, S.C.B. Methods developed for SELEX. Anal. Bioanal. Chem.; 2007; 387, pp. 171-182. [DOI: https://dx.doi.org/10.1007/s00216-006-0826-2]
43. Darmostuk, M.; Rimpelova, S.; Gbelcova, H.; Ruml, T. Current approaches in SELEX: An update to aptamer selection technology. Biotechnol. Adv.; 2015; 33, pp. 1141-1161. [DOI: https://dx.doi.org/10.1016/j.biotechadv.2015.02.008]
44. Bognar, Z.; Gyurcsanyi, R.E. Aptamers against immunoglobulins: Design, selection and bioanalytical applications. Int. J. Mol. Sci.; 2020; 21, 5748. [DOI: https://dx.doi.org/10.3390/ijms21165748]
45. Liu, Q.; Jin, C.; Wang, Y.; Fang, X.; Zhang, X.; Chen, Z.; Tan, W. Aptamer-conjugated nanomaterials for specific cancer cell recognition and targeted cancer therapy. NPG Asia Mater.; 2014; 6, e95. [DOI: https://dx.doi.org/10.1038/am.2014.12]
46. Zhou, Q.; Xu, Z.; Liu, Z. Molecularly imprinting-aptamer techniques and their applications in molecular recognition. Biosensors; 2022; 12, 576. [DOI: https://dx.doi.org/10.3390/bios12080576]
47. Hasanzadeh, M.; Shadjou, N.; de la Guardia, M. Aptamer-based assay of biomolecules: Recent advances in electro-analytical approach. TrAC Trends Anal. Chem.; 2017; 89, pp. 119-132. [DOI: https://dx.doi.org/10.1016/j.trac.2017.02.003]
48. Wu, D.; Gordon, C.K.L.; Shin, J.H.; Eisenstein, M.; Soh, H.T. Directed evolution of aptamer discovery technologies. Acc. Chem. Res.; 2022; 55, pp. 685-695. [DOI: https://dx.doi.org/10.1021/acs.accounts.1c00724]
49. Chen, M.; Yu, Y.; Jiang, F.; Zhou, J.; Li, Y.; Liang, C.; Dang, L.; Lu, A.; Zhang, G. Development of cell-SELEX technology and its application in cancer diagnosis and therapy. Int. J. Mol. Sci.; 2016; 17, 2079. [DOI: https://dx.doi.org/10.3390/ijms17122079]
50. Daniels, D.A.; Chen, H.; Hicke, B.J.; Swiderek, K.M.; Gold, L. A tenascin-C aptamer identified by tumor cell SELEX: Systematic evolution of ligands by exponential enrichment. Proc. Natl. Acad. Sci. USA; 2003; 100, pp. 15416-15421. [DOI: https://dx.doi.org/10.1073/pnas.2136683100]
51. Gong, M.; Wehmeyer, K.R.; Halsall, H.B.; Heineman, W.R. Detection of VEGF165 using an aptamer affinity probe in microchip capillary electrophoresis. Curr. Pharm. Anal.; 2009; 5, pp. 156-163. [DOI: https://dx.doi.org/10.2174/157341209788172933]
52. Song, W.; Song, Y.; Li, Q.; Fan, C.; Lan, X.; Jiang, D. Advances in aptamer-based nuclear imaging. Eur. J. Nucl. Med. Mol. Imaging; 2022; 49, pp. 2544-2559. [DOI: https://dx.doi.org/10.1007/s00259-022-05782-0]
53. Eilers, A.; Witt, S.; Walter, J. Aptamer-modified nanoparticles in medical applications. Adv. Biochem. Eng. Biotechnol.; 2020; 174, pp. 161-193. [DOI: https://dx.doi.org/10.1007/10_2020_124]
54. Shen, R.; Tan, J.; Yuan, Q. Chemically modified aptamers in biological analysis. ACS Appl. Bio. Mater.; 2020; 3, pp. 2816-2826. [DOI: https://dx.doi.org/10.1021/acsabm.0c00062]
55. Dinakar, Y.H.; Karole, A.; Parvez, S.; Jain, V.; Mudavath, S.L. Organ-restricted delivery through stimuli-responsive nanocarriers for lung cancer therapy. Life Sci.; 2022; 310, 121133. [DOI: https://dx.doi.org/10.1016/j.lfs.2022.121133]
56. Xin, Y.; Yin, M.; Zhao, L.; Meng, F.; Luo, L. Recent progress on nanoparticle-based drug delivery systems for cancer therapy. Cancer Biol. Med.; 2017; 14, pp. 228-241. [DOI: https://dx.doi.org/10.20892/j.issn.2095-3941.2017.0052]
57. Liu, K.; Jiang, X.; Hunziker, P. Carbohydrate-based amphiphilic nano delivery systems for cancer therapy. Nanoscale; 2016; 8, pp. 16091-16156. [DOI: https://dx.doi.org/10.1039/C6NR04489A]
58. Abdellatif, A.A.H.; Mohammed, H.A.; Khan, R.A.; Singh, V.; Bouazzaoui, A.; Yusuf, M.; Akhtar, N.; Khan, M.; Al-Subaiyel, A.; Mohammed, S.A.A. et al. Nano-scale delivery: A comprehensive review of nano-structured devices, preparative techniques, site-specificity designs, biomedical applications, commercial products, and references to safety, cellular uptake, and organ toxicity. Nanotechnol. Rev.; 2021; 10, pp. 1493-1559. [DOI: https://dx.doi.org/10.1515/ntrev-2021-0096]
59. Lohiya, G.; Katti, D.S. Carboxylated chitosan-mediated improved efficacy of mesoporous silica nanoparticle-based targeted drug delivery system for breast cancer therapy. Carbohyd. Polym.; 2022; 277, 118822. [DOI: https://dx.doi.org/10.1016/j.carbpol.2021.118822]
60. Hu, L.; Cui, J.; Wang, Y.; Jia, J. An ultrasensitive electrochemical biosensor for bisphenol a based on aptamer-modified MrGO@AuNPs and ssDNA-functionalized AuNP@mbs synergistic amplification. Chemosphere; 2022; 311, 137154. [DOI: https://dx.doi.org/10.1016/j.chemosphere.2022.137154]
61. Jiang, Y.; Zhao, W.; Zhou, H.; Zhang, Q.; Zhang, S. Atp-triggered intracellular in situ aggregation of a gold-nanoparticle-equipped triple-helix molecular switch for fluorescence imaging and photothermal tumor therapy. Langmuir; 2022; 38, pp. 3755-3764. [DOI: https://dx.doi.org/10.1021/acs.langmuir.1c03331]
62. Kadkhoda, J.; Aghanejad, A.; Safari, B.; Barar, J.; Rasta, S.H.; Davaran, S. Aptamer-conjugated gold nanoparticles for targeted paclitaxel delivery and photothermal therapy in breast cancer. J. Drug Deliv. Sci. Tec.; 2022; 67, 102954. [DOI: https://dx.doi.org/10.1016/j.jddst.2021.102954]
63. Zhao, M.-X.; Zeng, E.-Z.; Zhu, B.-J. The biological applications of inorganic nanoparticle drug carriers. Chemnanomat; 2015; 1, pp. 82-91. [DOI: https://dx.doi.org/10.1002/cnma.201500036]
64. Zhao, Q.; Liu, J.; Zhu, W.; Sun, C.; Di, D.; Zhang, Y.; Wang, P.; Wang, Z.; Wang, S. Dual-stimuli responsive hyaluronic acid-conjugated mesoporous silica for targeted delivery to CD44-overexpressing cancer cells. Acta Biomater.; 2015; 23, pp. 147-156. [DOI: https://dx.doi.org/10.1016/j.actbio.2015.05.010]
65. Abraham, T.; McGovern, C.O.; Linton, S.S.; Wilczynski, Z.; Adair, J.H.; Matters, G.L. Aptamer-targeted calcium phosphosilicate nanoparticles for effective imaging of pancreatic and prostate cancer. Int. J. Nanomed.; 2021; 16, pp. 2297-2309. [DOI: https://dx.doi.org/10.2147/IJN.S295740]
66. Liu, H.-J.; Xu, P. Smart mesoporous silica nanoparticles for protein delivery. Nanomaterials; 2019; 9, 511. [DOI: https://dx.doi.org/10.3390/nano9040511]
67. Wang, Y.; Zhao, Q.; Han, N.; Bai, L.; Li, J.; Liu, J.; Che, E.; Hu, L.; Zhang, Q.; Jiang, T. et al. Mesoporous silica nanoparticles in drug delivery and biomedical applications. Nanomedicine; 2015; 11, pp. 313-327. [DOI: https://dx.doi.org/10.1016/j.nano.2014.09.014]
68. Stephen, S.; Gorain, B.; Choudhury, H.; Chatterjee, B. Exploring the role of mesoporous silica nanoparticle in the development of novel drug delivery systems. Drug Deliv. Transl. Res.; 2022; 12, pp. 105-123. [DOI: https://dx.doi.org/10.1007/s13346-021-00935-4]
69. Shen, S.-C.; Ng, W.K.; Chia, L.S.O.; Dong, Y.-C.; Tan, R.B.H. Applications of mesoporous materials as excipients for innovative drug delivery and formulation. Curr. Pharm. Des.; 2013; 19, pp. 6270-6289. [DOI: https://dx.doi.org/10.2174/1381612811319350005]
70. Hanafi-Bojd, M.Y.; Moosavian Kalat, S.A.; Taghdisi, S.M.; Ansari, L.; Abnous, K.; Malaekeh-Nikouei, B. MUC1 aptamer-conjugated mesoporous silica nanoparticles effectively target breast cancer cells. Drug Dev. Ind. Pharm.; 2018; 44, pp. 13-18. [DOI: https://dx.doi.org/10.1080/03639045.2017.1371734]
71. Xie, X.; Li, F.; Zhang, H.; Lu, Y.; Lian, S.; Lin, H.; Gao, Y.; Jia, L. EpCAM aptamer-functionalized mesoporous silica nanoparticles for efficient colon cancer cell-targeted drug delivery. Eur. J. Pharm. Sci.; 2016; 83, pp. 28-35. [DOI: https://dx.doi.org/10.1016/j.ejps.2015.12.014]
72. Vivo-Llorca, G.; Candela-Noguera, V.; Alfonso, M.; García-Fernández, A.; Orzáez, M.; Sancenón, F.; Martínez-Máñez, R. MUC1 aptamer-capped mesoporous silica nanoparticles for navitoclax resistance overcoming in triple-negative breast cancer. Chemistry; 2020; 26, pp. 16318-16327. [DOI: https://dx.doi.org/10.1002/chem.202001579]
73. Pascual, L.; Cerqueira-Coutinho, C.; García-Fernández, A.; de Luis, B.; Bernardes, E.S.; Albernaz, M.S.; Missailidis, S.; Martínez-Máñez, R.; Santos-Oliveira, R.; Orzaez, M. et al. MUC1 aptamer-capped mesoporous silica nanoparticles for controlled drug delivery and radio-imaging applications. Nanomedicine; 2017; 13, pp. 2495-2505. [DOI: https://dx.doi.org/10.1016/j.nano.2017.08.006]
74. Li, Y.; Duo, Y.; Bao, S.; He, L.; Ling, K.; Luo, J.; Zhang, Y.; Huang, H.; Zhang, H.; Yu, X. EpCAM aptamer-functionalized polydopamine-coated mesoporous silica nanoparticles loaded with DM1 for targeted therapy in colorectal cancer. Int. J. Nanomed.; 2017; 12, pp. 6239-6257. [DOI: https://dx.doi.org/10.2147/IJN.S143293]
75. Wang, K.; Yao, H.; Meng, Y.; Wang, Y.; Yan, X.; Huang, R. Specific aptamer-conjugated mesoporous silica–carbon nanoparticles for HER2-targeted chemo-photothermal combined therapy. Acta Biomater.; 2015; 16, pp. 196-205. [DOI: https://dx.doi.org/10.1016/j.actbio.2015.01.002]
76. Yang, Y.; Zhao, W.; Tan, W.; Lai, Z.; Fang, D.; Jiang, L.; Zuo, C.; Yang, N.; Lai, Y. An efficient cell-targeting drug delivery system based on aptamer-modified mesoporous silica nanoparticles. Nanoscale Res. Lett.; 2019; 14, 390. [DOI: https://dx.doi.org/10.1186/s11671-019-3208-3]
77. Sakhtianchi, R.; Darvishi, B.; Mirzaie, Z.; Dorkoosh, F.; Shanehsazzadeh, S.; Dinarvand, R. Pegylated magnetic mesoporous silica nanoparticles decorated with AS1411 aptamer as a targeting delivery system for cytotoxic agents. Pharm. Dev. Technol.; 2019; 24, pp. 1063-1075. [DOI: https://dx.doi.org/10.1080/10837450.2019.1569678]
78. Iranpour, S.; Bahrami, A.R.; Nekooei, S.; Saljooghi, A.S.; Matin, M.M. Improving anti-cancer drug delivery performance of magnetic mesoporous silica nanocarriers for more efficient colorectal cancer therapy. J. Nanobiotechnol.; 2021; 19, 314. [DOI: https://dx.doi.org/10.1186/s12951-021-01056-3]
79. Li, Y.; Duo, Y.; Zhai, P.; He, L.; Zhong, K.; Zhang, Y.; Huang, K.; Luo, J.; Zhang, H.; Yu, X. Dual targeting delivery of miR-328 by functionalized mesoporous silica nanoparticles for colorectal cancer therapy. Nanomedicine; 2018; 13, pp. 1753-1772. [DOI: https://dx.doi.org/10.2217/nnm-2017-0353]
80. Li, L.-L.; Yin, Q.; Cheng, J.; Lu, Y. Polyvalent mesoporous silica nanoparticle-aptamer bioconjugates target breast cancer cells. Adv. Healthc. Mater.; 2012; 1, pp. 567-572. [DOI: https://dx.doi.org/10.1002/adhm.201200116]
81. Chomoucka, J.; Drbohlavova, J.; Huska, D.; Adam, V.; Kizek, R.; Hubalek, J. Magnetic nanoparticles and targeted drug delivering. Pharmacol. Res.; 2010; 62, pp. 144-149. [DOI: https://dx.doi.org/10.1016/j.phrs.2010.01.014]
82. Wong, J.; Prout, J.; Seifalian, A. Magnetic nanoparticles: New perspectives in drug delivery. Curr. Pharm. Des.; 2017; 23, pp. 2908-2917. [DOI: https://dx.doi.org/10.2174/1381612823666170215104659]
83. Kaliamurthi, S.; Demir-Korkmaz, A.; Selvaraj, G.; Gokce-Polat, E.; Wei, Y.-K.; Almessiere, M.A.; Baykal, A.; Gu, K.; Wei, D.-Q. Viewing the emphasis on state-of-the-art magnetic nanoparticies: Synthesis, physical properties, and applications in cancer theranostics. Curr. Pharm. Des.; 2019; 25, pp. 1505-1523. [DOI: https://dx.doi.org/10.2174/1381612825666190523105004]
84. Mou, X.; Ali, Z.; Li, S.; He, N. Applications of magnetic nanoparticles in targeted drug delivery system. J. Nanosci. Nanotechnol.; 2015; 15, pp. 54-62. [DOI: https://dx.doi.org/10.1166/jnn.2015.9585]
85. Jose, J.; Kumar, R.; Harilal, S.; Mathew, G.E.; Parambi, D.G.T.; Prabhu, A.; Uddin, M.S.; Aleya, L.; Kim, H.; Mathew, B. Magnetic nanoparticles for hyperthermia in cancer treatment: An emerging tool. Environ. Sci. Pollut. Res. Int.; 2020; 27, pp. 19214-19225. [DOI: https://dx.doi.org/10.1007/s11356-019-07231-2]
86. Sadhasivam, J.; Sugumaran, A. Magnetic nanocarriers: Emerging tool for the effective targeted treatment of lung cancer. J. Drug Deliv. Sci. Technol.; 2020; 55, 101493. [DOI: https://dx.doi.org/10.1016/j.jddst.2019.101493]
87. Sivakumar, B.; Aswathy, R.G.; Nagaoka, Y.; Iwai, S.; Venugopal, K.; Kato, K.; Yoshida, Y.; Maekawa, T.; Sakthi Kumar, D.N. Aptamer conjugated theragnostic multifunctional magnetic nanoparticles as a nanoplatform for pancreatic cancer therapy. RSC Adv.; 2013; 3, pp. 20579-20598. [DOI: https://dx.doi.org/10.1039/c3ra42645a]
88. Kolovskaya, O.S.; Zamay, T.N.; Zamay, G.S.; Babkin, V.A.; Medvedeva, E.N.; Neverova, N.A.; Kirichenko, A.K.; Zamay, S.S.; Lapin, I.N.; Morozov, E.V. et al. Aptamer-conjugated superparamagnetic ferroarabinogalactan nanoparticles for targeted magnetodynamic therapy of cancer. Cancers; 2020; 12, 216. [DOI: https://dx.doi.org/10.3390/cancers12010216]
89. Zhao, C.; Song, X.; Jin, W.; Wu, F.; Zhang, Q.; Zhang, M.; Zhou, N.; Shen, J. Image-guided cancer therapy using aptamer-functionalized cross-linked magnetic-responsive Fe3O4@carbon nanoparticles. Anal. Chim. Acta; 2019; 1056, pp. 108-116. [DOI: https://dx.doi.org/10.1016/j.aca.2018.12.045]
90. Mohaghegh, S.; Tarighatnia, A.; Omidi, Y.; Barar, J.; Aghanejad, A.; Adibkia, K. Multifunctional magnetic nanoparticles for MRI-guided co-delivery of erlotinib and L-asparaginase to ovarian cancer. J. Microencapsul.; 2022; 39, pp. 394-408. [DOI: https://dx.doi.org/10.1080/02652048.2022.2094487]
91. Zhao, J.; Tu, K.; Liu, Y.; Qin, Y.; Wang, X.; Qi, L.; Shi, D. Photo-controlled aptamers delivery by dual surface gold-magnetic nanoparticles for targeted cancer therapy. Mater. Sci. Eng. C Mater. Biol. Appl.; 2017; 80, pp. 88-92. [DOI: https://dx.doi.org/10.1016/j.msec.2017.04.044]
92. Kesharwani, P.; Gothwal, A.; Iyer, A.K.; Jain, K.; Chourasia, M.K.; Gupta, U. Dendrimer nanohybrid carrier systems: An expanding horizon for targeted drug and gene delivery. Drug Discov. Today; 2018; 23, pp. 300-314. [DOI: https://dx.doi.org/10.1016/j.drudis.2017.06.009]
93. Bhatia, R.; Sharma, A.; Narang, R.K.; Rawal, R.K. Recent nanocarrier approaches for targeted drug delivery in cancer therapy. Curr. Mol. Pharmacol.; 2021; 14, pp. 350-366. [DOI: https://dx.doi.org/10.2174/1874467213666200730114943]
94. Yamada, Y. A nanocarrier system for mitochondrial delivery targeted to a pancreatic beta cell. Yakugaku Zasshi; 2019; 139, pp. 41-45. [DOI: https://dx.doi.org/10.1248/yakushi.18-00163-1]
95. El Kadib, A. Chitosan as a sustainable organocatalyst: A concise overview. Chemsuschem; 2015; 8, pp. 217-244. [DOI: https://dx.doi.org/10.1002/cssc.201402718]
96. Kalita, P.; Ahmed, A.B.; Sen, S.; Chakraborty, R. A comprehensive review on polysaccharides with hypolipidemic activity: Occurrence, chemistry and molecular mechanism. Int. J. Biol. Macromol.; 2022; 206, pp. 681-698. [DOI: https://dx.doi.org/10.1016/j.ijbiomac.2022.02.189]
97. Zhou, Y.; Petrova, S.P.; Edgar, K.J. Chemical synthesis of polysaccharide-protein and polysaccharide-peptide conjugates: A review. Carbohydr. Polym.; 2021; 274, 118662. [DOI: https://dx.doi.org/10.1016/j.carbpol.2021.118662]
98. Koyyada, A.; Orsu, P. Natural gum polysaccharides as efficient tissue engineering and drug delivery biopolymers. J. Drug Deliv. Sci. Technol.; 2021; 63, 102431. [DOI: https://dx.doi.org/10.1016/j.jddst.2021.102431]
99. Qiu, A.; Wang, Y.; Zhang, G.; Wang, H. Natural polysaccharide-based nanodrug delivery systems for treatment of diabetes. Polymers; 2022; 14, 3217. [DOI: https://dx.doi.org/10.3390/polym14153217]
100. Zhang, Y.; Dong, L.; Liu, L.; Wu, Z.; Pan, D.; Liu, L. Recent advances of stimuli-responsive polysaccharide hydrogels in delivery systems: A review. J. Agric. Food Chem.; 2022; 70, pp. 6300-6316. [DOI: https://dx.doi.org/10.1021/acs.jafc.2c01080]
101. Esfandyari-Manesh, M.; Mohammadi, A.; Atyabi, F.; Nabavi, S.M.; Ebrahimi, S.M.; Shahmoradi, E.; Varnamkhasti, B.S.; Ghahremani, M.H.; Dinarvand, R. Specific targeting delivery to MUC1 overexpressing tumors by albumin-chitosan nanoparticles conjugated to DNA aptamer. Int. J. Pharm.; 2016; 515, pp. 607-615. [DOI: https://dx.doi.org/10.1016/j.ijpharm.2016.10.066]
102. Koo, O.M.; Rubinstein, I.; Onyuksel, H. Role of nanotechnology in targeted drug delivery and imaging: A concise review. Nanomedicine; 2005; 1, pp. 193-212. [DOI: https://dx.doi.org/10.1016/j.nano.2005.06.004]
103. Kang, K.W.; Chun, M.-K.; Kim, O.; Subedi, R.K.; Ahn, S.-G.; Yoon, J.-H.; Choi, H.-K. Doxorubicin-loaded solid lipid nanoparticles to overcome multidrug resistance in cancer therapy. Nanomedicine; 2010; 6, pp. 210-213. [DOI: https://dx.doi.org/10.1016/j.nano.2009.12.006]
104. Li, L.; Hou, J.; Liu, X.; Guo, Y.; Wu, Y.; Zhang, L.; Yang, Z. Nucleolin-targeting liposomes guided by aptamer AS1411 for the delivery of siRNA for the treatment of malignant melanomas. Biomaterials; 2014; 35, pp. 3840-3850. [DOI: https://dx.doi.org/10.1016/j.biomaterials.2014.01.019]
105. Shakib, Z.; Mahmoudi, A.; Moosavian, S.A.; Malaekeh-Nikouei, B. PEGylated solid lipid nanoparticles functionalized by aptamer for targeted delivery of docetaxel in mice bearing C26 tumor. Drug Dev. Ind. Pharm.; 2022; 48, pp. 69-78. [DOI: https://dx.doi.org/10.1080/03639045.2022.2095398]
106. Jianghong, L.; Tingting, M.; Yingping, Z.; Tong, Y.; Lanxia, Z.; Jingwen, L.; Wentao, Z.; Pengbo, C.; Hong, Y.; Fuqiang, H. Aptamer and peptide-modified lipid-based drug delivery systems in application of combined sequential therapy of hepatocellular carcinoma. ACS Biomater. Sci. Eng.; 2021; 7, pp. 2558-2568. [DOI: https://dx.doi.org/10.1021/acsbiomaterials.1c00357]
107. Li, J.; Li, Q.; He, M.; Ding, F.; Cai, L.; Zhao, M.; Dong, L.; Wang, Q.; Xu, K. AS1411 aptamer-modified theranostic liposomes co-encapsulating manganese oxide nano-contrast agent and paclitaxel for MRI and therapy of cancer. RSC Adv.; 2019; 9, pp. 34837-34846. [DOI: https://dx.doi.org/10.1039/C9RA06878C]
108. Sun, X.; Chen, Y.; Zhao, H.; Qiao, G.; Liu, M.; Zhang, C.; Cui, D.; Ma, L. Dual-modified cationic liposomes loaded with paclitaxel and survivin siRNA for targeted imaging and therapy of cancer stem cells in brain glioma. Drug Deliv.; 2018; 25, pp. 1718-1727. [DOI: https://dx.doi.org/10.1080/10717544.2018.1494225]
109. Darabi, F.; Saidijam, M.; Nouri, F.; Mahjub, R.; Soleimani, M. Anti-CD44 and EGFR dual-targeted solid lipid nanoparticles for delivery of doxorubicin to triple-negative breast cancer cell line: Preparation, statistical optimization, and in vitro characterization. Biomed. Res. Int.; 2022; 2022, 6253978. [DOI: https://dx.doi.org/10.1155/2022/6253978]
110. Nie, L.; Sun, S.; Sun, M.; Zhou, Q.; Zhang, Z.; Zheng, L.; Wang, L. Synthesis of aptamer-PEI-g-PEG modified gold nanoparticles loaded with doxorubicin for targeted drug delivery. JoVE-J. Vis. Exp.; 2020; 160, e61139. [DOI: https://dx.doi.org/10.3791/61139]
111. Shahrad, S.; Rajabi, M.; Javadi, H.; Karimi Zarchi, A.A.; Darvishi, M.H. Targeting lung cancer cells with MUC1 aptamer-functionalized PLA-PEG nanocarriers. Sci. Rep.; 2022; 12, 4718. [DOI: https://dx.doi.org/10.1038/s41598-022-08759-z]
112. Zhang, Y.; Li, C.; Jia, R.; Gao, R.; Zhao, Y.; Ji, Q.; Cai, J.; Li, Q.; Wang, Y. PEG-poly(amino acid)s/EpCAM aptamer multifunctional nanoparticles arrest the growth and metastasis of colorectal cancer. Biomater. Sci.; 2021; 9, pp. 3705-3717. [DOI: https://dx.doi.org/10.1039/D1BM00160D]
113. Yang, Y.; Zhu, W.; Cheng, L.; Cai, R.; Yi, X.; He, J.; Pan, X.; Yang, L.; Yang, K.; Liu, Z. et al. Tumor microenvironment (TME)-activatable circular aptamer-PEG as an effective hierarchical-targeting molecular medicine for photodynamic therapy. Biomaterials; 2020; 246, 119971. [DOI: https://dx.doi.org/10.1016/j.biomaterials.2020.119971]
114. Luo, X.; Yang, Y.; Kong, F.; Zhang, L.; Wei, K. CD30 aptamer-functionalized PEG-PLGA nanoparticles for the superior delivery of doxorubicin to anaplastic large cell lymphoma cells. Int. J. Pharmaceut.; 2019; 564, pp. 340-349. [DOI: https://dx.doi.org/10.1016/j.ijpharm.2019.04.013]
115. Jiao, J.; Zou, Q.; Zou, M.H.; Guo, R.M.; Zhu, S.; Zhang, Y. Aptamer-modified PLGA nanoparticle delivery of triplex forming oligonucleotide for targeted prostate cancer therapy. Neoplasma; 2016; 63, pp. 569-575. [DOI: https://dx.doi.org/10.4149/neo_2016_410]
116. Chen, W.; Yang, S.; Wei, X.; Yang, Z.; Liu, D.; Pu, X.; He, S.; Zhang, Y. Construction of aptamer-siRNA chimera/PEI/5-FU/carbon nanotube/collagen membranes for the treatment of peritoneal dissemination of drug-resistant gastric cancer. Adv. Healthc. Mater.; 2020; 9, 2001153. [DOI: https://dx.doi.org/10.1002/adhm.202001153]
117. Jiang, H.; Wang, L.-B.; Zhang, Y.-T.; Dong, M.; Li, J.; Wang, J.-D. An entropy-driven three-dimensional multipedal-DNA walker for ultrasensitive detection of cancer cells. Anal. Chim. Acta; 2022; 1228, 340299. [DOI: https://dx.doi.org/10.1016/j.aca.2022.340299]
118. Gong, H.; Dai, Q.; Peng, P. Cell-membrane-anchored DNA logic-gated nanoassemblies for in situ extracellular bioimaging. ACS Appl. Mater. Interfaces; 2022; 14, pp. 43026-43034. [DOI: https://dx.doi.org/10.1021/acsami.2c13735]
119. Guo, W.; Gao, H.; Li, H.; Ge, S.; Zhang, F.; Wang, L.; Shi, H.; Han, A. Self-assembly of a multifunction DNA tetrahedron for effective delivery of aptamer PL1 and PCSK9 siRNA potentiate immune checkpoint therapy for colorectal cancer. ACS Appl. Mater. Interfaces; 2022; 14, pp. 31634-31644. [DOI: https://dx.doi.org/10.1021/acsami.2c06001]
120. Li, R.; Wu, X.; Li, J.; Lu, X.; Zhao, R.C.; Liu, J.; Ding, B. A covalently conjugated branched DNA aptamer cluster-based nanoplatform for efficiently targeted drug delivery. Nanoscale; 2022; 14, pp. 9369-9378. [DOI: https://dx.doi.org/10.1039/D2NR01252A]
121. He, Z.; Wang, Q.; Zhang, N.; Yan, J.; Li, L.; Cao, J.; He, B. Gold nanorods/tetrahedral DNA composites for chemo-photothermal therapy. Regen. Biomater.; 2022; 9, rbac032. [DOI: https://dx.doi.org/10.1093/rb/rbac032]
122. Li, C.H.; Lv, W.Y.; Yang, F.F.; Zhen, S.J.; Huang, C.Z. Simultaneous imaging of dual micrornas in cancer cells through catalytic hairpin assembly on a DNA tetrahedron. ACS Appl. Mater. Interfaces; 2022; 14, pp. 12059-12067. [DOI: https://dx.doi.org/10.1021/acsami.1c23227]
123. Ma, W.; Yang, Y.; Zhu, J.; Jia, W.; Zhang, T.; Liu, Z.; Chen, X.; Lin, Y. Biomimetic nanoerythrosome-coated aptamer–DNA tetrahedron/maytansine conjugates: pH-responsive and targeted cytotoxicity for HER2-positive breast cancer. Adv. Mater.; 2022; e2109609. [DOI: https://dx.doi.org/10.1002/adma.202109609]
124. Tang, W.; Han, L.; Duan, S.; Lu, X.; Wang, Y.; Wu, X.; Liu, J.; Ding, B. An aptamer-modified DNA tetrahedron-based nanogel for combined chemo/gene therapy of multidrug-resistant tumors. ACS Appl. Bio Mater.; 2021; 4, pp. 7701-7707. [DOI: https://dx.doi.org/10.1021/acsabm.1c00933]
125. Wang, F.; Zhou, Y.; Cheng, S.; Lou, J.; Zhang, X.; He, Q.; Huang, N.; Cheng, Y. Gint4.T-modified DNA tetrahedrons loaded with doxorubicin inhibits glioma cell proliferation by targeting PDGFRΒ. Nanoscale Res. Lett.; 2020; 15, 150. [DOI: https://dx.doi.org/10.1186/s11671-020-03377-y]
126. Xie, X.; Zhang, Y.; Ma, W.; Shao, X.; Zhan, Y.; Mao, C.; Zhu, B.; Zhou, Y.; Zhao, H.; Cai, X. Potent anti-angiogenesis and anti-tumour activity of pegaptanib-loaded tetrahedral DNA nanostructure. Cell Prolif.; 2019; 52, e12662. [DOI: https://dx.doi.org/10.1111/cpr.12662]
127. Zhan, Y.; Ma, W.; Zhang, Y.; Mao, C.; Shao, X.; Xie, X.; Wang, F.; Liu, X.; Li, Q.; Lin, Y. DNA-based nanomedicine with targeting and enhancement of therapeutic efficacy of breast cancer cells. ACS Appl. Mater. Interfaces; 2019; 11, pp. 15354-15365. [DOI: https://dx.doi.org/10.1021/acsami.9b03449]
128. Liu, X.; Wu, L.; Wang, L.; Jiang, W. A dual-targeting DNA tetrahedron nanocarrier for breast cancer cell imaging and drug delivery. Talanta; 2018; 179, pp. 356-363. [DOI: https://dx.doi.org/10.1016/j.talanta.2017.11.034]
129. Sun, P.; Zhang, N.; Tang, Y.; Yang, Y.; Chu, X.; Zhao, Y. SL2B aptamer and folic acid dual-targeting DNA nanostructures for synergic biological effect with chemotherapy to combat colorectal cancer. Int. J. Nanomed.; 2017; 12, pp. 2657-2672. [DOI: https://dx.doi.org/10.2147/IJN.S132929]
130. Dai, B.; Hu, Y.; Duan, J.; Yang, X.-D. Aptamer-guided DNA tetrahedron as a novel targeted drug delivery system for MUC1-expressing breast cancer cells in vitro. Oncotaget; 2016; 7, pp. 38257-38269. [DOI: https://dx.doi.org/10.18632/oncotarget.9431]
131. Ma, J.; Huang, L.; Hu, D.; Zeng, S.; Han, Y.; Shen, H. The role of the tumor microbe microenvironment in the tumor immune microenvironment: Bystander, activator, or inhibitor?. J. Exp. Clin. Cancer Res.; 2021; 40, 327. [DOI: https://dx.doi.org/10.1186/s13046-021-02128-w]
132. Xiao, Y.; Yu, D. Tumor microenvironment as a therapeutic target in cancer. Pharmacol. Therapeut.; 2021; 221, 107753. [DOI: https://dx.doi.org/10.1016/j.pharmthera.2020.107753]
133. Xie, S.; Wang, Z.; Fu, T.; Zheng, L.; Wu, H.; He, L.; Huang, H.; Yang, C.; Wang, R.; Qian, X. et al. Engineering aptamers with selectively enhanced biostability in the tumor microenvironment. Angew. Chem. Int. Ed.; 2022; 61, e202201220. [DOI: https://dx.doi.org/10.1002/anie.202201220]
134. Bagheri, E.; Alibolandi, M.; Abnous, K.; Taghdisi, S.M.; Ramezani, M. Targeted delivery and controlled release of doxorubicin to cancer cells by smart ATP-responsive Y-shaped DNA structure-capped mesoporous silica nanoparticles. J. Mater. Chem. B; 2021; 9, pp. 1351-1363. [DOI: https://dx.doi.org/10.1039/D0TB01960G]
135. Esawi, E.; Alshaer, W.; Mahmoud, I.S.; Alqudah, D.A.; Azab, B.; Awidi, A. Aptamer-aptamer chimera for targeted delivery and ATP-responsive release of doxorubicin into cancer cells. Int. J. Mol. Sci.; 2021; 22, 12940. [DOI: https://dx.doi.org/10.3390/ijms222312940]
136. Matthews, G.M.; Howarth, G.S.; Butler, R.N. Nutrient and antioxidant modulation of apoptosis in gastric and colon cancer cells. Cancer Biol. Ther.; 2006; 5, pp. 569-572. [DOI: https://dx.doi.org/10.4161/cbt.5.6.2868]
137. Narayanankutty, A.; Job, J.T.; Narayanankutty, V. Giutathione, an antioxidant tripeptide: Dual roles in carcinogenesis and chemoprevention. Curr. Protein Pept. Sci.; 2019; 20, pp. 907-917. [DOI: https://dx.doi.org/10.2174/1389203720666190206130003]
138. Estrela, J.M.; Ortega, A.; Obrador, E. Glutathione in cancer biology and therapy. Crit. Rev. Clin. Lab. Sci.; 2006; 43, pp. 143-181. [DOI: https://dx.doi.org/10.1080/10408360500523878]
139. Niu, B.; Liao, K.; Zhou, Y.; Wen, T.; Quan, G.; Pan, X.; Wu, C. Application of glutathione depletion in cancer therapy: Enhanced ROS-based therapy, ferroptosis, and chemotherapy. Biomaterials; 2021; 277, 121110. [DOI: https://dx.doi.org/10.1016/j.biomaterials.2021.121110]
140. Bala, J.; Bhaskar, A.; Varshney, A.; Singh, A.K.; Dey, S.; Yadava, P. In vitro selected RNA aptamer recognizing glutathione induces ROS-mediated apoptosis in the human breast cancer cell line MCF 7. RNA Biol.; 2011; 8, pp. 101-111. [DOI: https://dx.doi.org/10.4161/rna.8.1.14116]
141. An, S.; Lu, X.; Zhao, W.; Sun, T.; Zhang, Y.; Lu, Y.; Jiang, C. Amino acid metabolism abnormity and microenvironment variation mediated targeting and controlled glioma chemotherapy. Small; 2016; 12, pp. 5633-5645. [DOI: https://dx.doi.org/10.1002/smll.201601249]
142. Guo, Y.; Wang, Y.; Li, S.; Niu, L.; Wei, D.; Zhang, S. DNA-spheres decorated with magnetic nanocomposites based on terminal transfer reactions for versatile target detection and cellular targeted drug delivery. Chem. Commun.; 2017; 53, pp. 4826-4829. [DOI: https://dx.doi.org/10.1039/C7CC00310B]
143. Touyz, R.M. Reactive oxygen species in vascular biology: Role in arterial hypertension. Expert Rev. Cardiovasc. Ther.; 2003; 1, pp. 91-106. [DOI: https://dx.doi.org/10.1586/14779072.1.1.91]
144. Khan, A.U.; Wilson, T. Reactive oxygen species as cellular messengers. Chem. Biol.; 1995; 2, pp. 437-445. [DOI: https://dx.doi.org/10.1016/1074-5521(95)90259-7]
145. Baglam, T.; Sari, M.; Yazici, Z.M.; Yuksel, M.; Uneri, C. Chemiluminescence assay of reactive oxygen species in laryngeal cancer. J. Laryngol. Otol.; 2010; 124, pp. 1091-1094. [DOI: https://dx.doi.org/10.1017/S0022215110000988]
146. Tamura, M.; Matsui, H.; Tomita, T.; Sadakata, H.; Indo, H.P.; Majima, H.J.; Kaneko, T.; Hyodo, I. Mitochondrial reactive oxygen species accelerate gastric cancer cell invasion. J. Clin. Biochem. Nutr.; 2014; 54, pp. 12-17. [DOI: https://dx.doi.org/10.3164/jcbn.13-36]
147. Zhang, H.; Li, B.; Sun, Z.; Zhou, H.; Zhang, S. Integration of intracellular telomerase monitoring by electrochemiluminescence technology and targeted cancer therapy by reactive oxygen species. Chem. Sci.; 2017; 8, pp. 8025-8029. [DOI: https://dx.doi.org/10.1039/C7SC03772D]
148. Liu, W.; Zhang, K.; Zhuang, L.; Liu, J.; Zeng, W.; Shi, J.; Zhang, Z. Aptamer/photosensitizer hybridized mesoporous MnO2 based tumor cell activated ROS regulator for precise photodynamic therapy of breast cancer. Colloids Surf. B Biointerfaces; 2019; 184, 110536. [DOI: https://dx.doi.org/10.1016/j.colsurfb.2019.110536]
149. Ghizoni, J.S.; Nichele, R.; de Oliveira, M.T.; Pamato, S.; Pereira, J.R. The utilization of saliva as an early diagnostic tool for oral cancer: Microrna as a biomarker. Clin. Transl. Oncol.; 2020; 22, pp. 804-812. [DOI: https://dx.doi.org/10.1007/s12094-019-02210-y]
150. Zhang, W.; Zhang, X.J.; Chao, S.Y.; Chen, S.J.; Zhang, Z.J.; Zhao, J.; Lv, Y.N.; Yao, J.J.; Bai, Y.Y. Update on urine as a biomarker in cancer: A necessary review of an old story. Expert Rev. Mol. Diagn.; 2020; 20, pp. 477-488. [DOI: https://dx.doi.org/10.1080/14737159.2020.1743687]
151. Conduit, C.; Tran, B. Improving outcomes in germ cell cancers using miRNA. Ther. Adv. Oncol.; 2021; 13, 17588359211027826. [DOI: https://dx.doi.org/10.1177/17588359211027826]
152. Hobani, Y.H. Focally amplified long non-coding RNA in epithelial cancer as a potential biomarker and therapeutic target. Biomark. Med.; 2021; 15, pp. 1797-1808. [DOI: https://dx.doi.org/10.2217/bmm-2021-0455]
153. Liu, H.; Zhang, Y.; Li, L.; Cao, J.; Guo, Y.; Wu, Y.; Gao, W. Fascin actin-bundling protein 1 in human cancer: Promising biomarker or therapeutic target?. Mol. Ther.-Oncolyt.; 2021; 20, pp. 240-264. [DOI: https://dx.doi.org/10.1016/j.omto.2020.12.014]
154. Sharma, P.C.; Gupta, A. MicroRNAs: Potential biomarkers for diagnosis and prognosis of different cancers. Transl. Cancer Res.; 2020; 9, pp. 5798-5818. [DOI: https://dx.doi.org/10.21037/tcr-20-1294]
155. Jia, W.; Ren, C.; Wang, L.; Zhu, B.; Jia, W.; Gao, M.; Zeng, F.; Zeng, L.; Xia, X.; Zhang, X. et al. CD109 is identified as a potential nasopharyngeal carcinoma biomarker using aptamer selected by cell-SELEX. Oncotarget; 2016; 7, pp. 55328-55342. [DOI: https://dx.doi.org/10.18632/oncotarget.10530]
156. Xu, P.; Shao, M.; Jia, R.; Li, W.; Du, Z.; Han, Y. Peroxiredoxin-4 as a potential biomarker of early gastric cancer screened by cell-SELEX. Transl. Cancer Res.; 2017; 6, pp. 293-303. [DOI: https://dx.doi.org/10.21037/tcr.2017.03.72]
157. Guo, Y.; Li, K.; Gao, Y.; Zhao, S.; Shi, M.; Li, J.; Liu, Z.; Wang, Z.; He, L. CLEC3B identified as a potential lung cancer biomarker in serum by aptamer-capture technology. Chemistryselect; 2021; 6, pp. 5640-5645. [DOI: https://dx.doi.org/10.1002/slct.202100605]
158. Baba, T.; Convery, P.A.; Matsumura, N.; Whitaker, R.S.; Kondoh, E.; Perry, T.; Huang, Z.; Bentley, R.C.; Mori, S.; Fujii, S. et al. Epigenetic regulation of CD133 and tumorigenicity of CD133+ ovarian cancer cells. Oncogene; 2009; 28, pp. 209-218. [DOI: https://dx.doi.org/10.1038/onc.2008.374]
159. Yang, Z.-L.; Zheng, Q.; Yan, J.; Pan, Y.; Wang, Z.-G. Upregulated CD133 expression in tumorigenesis of colon cancer cells. World J. Gastroenterol.; 2011; 17, pp. 932-937. [DOI: https://dx.doi.org/10.3748/wjg.v17.i7.932]
160. Feng, J.-M.; Miao, Z.-H.; Jiang, Y.; Chen, Y.; Li, J.-X.; Tong, L.-J.; Zhang, J.; Huang, Y.-R.; Ding, J. Characterization of the conversion between CD133+ and CD133− cells in colon cancer SW620 cell line. Cancer Biol. Ther.; 2012; 13, pp. 1396-1406. [DOI: https://dx.doi.org/10.4161/cbt.22000]
161. Gharagozloo, M.; Mirzaei, H.R.; Bagherpour, B.; Rezaei, A.; Kalantari, H.; Sanei, M.H.; Hosseini, M.; Mohajeri, G.; Tabatabai, A.; Hashemi, M. Cell cycle analysis of the CD133 and CD133− cells isolated from human colorectal cancer. J. Cancer Res. Ther.; 2012; 8, pp. 399-403. [DOI: https://dx.doi.org/10.4103/0973-1482.103520]
162. Huang, P.; Watanabe, M.; Kaku, H.; Ueki, H.; Noguchi, H.; Sugimoto, M.; Hirata, T.; Yamada, H.; Takei, K.; Zheng, S. et al. Cancer stem cell-like characteristics of a CD133+ subpopulation in the J82 human bladder cancer cell line. Mol. Clin. Oncol.; 2013; 1, pp. 180-184. [DOI: https://dx.doi.org/10.3892/mco.2012.29]
163. Hashimoto, K.; Aoyagi, K.; Isobe, T.; Kouhuji, K.; Shirouzu, K. Expression of CD133 in the cytoplasm is associated with cancer progression and poor prognosis in gastric cancer. Gastric Cancer; 2014; 17, pp. 97-106. [DOI: https://dx.doi.org/10.1007/s10120-013-0255-9]
164. Tan, Y.; Chen, B.; Xu, W.; Zhao, W.; Wu, J. Clinicopathological significance of CD133 in lung cancer: A meta-analysis. Mol. Clin. Oncol.; 2014; 2, pp. 111-115. [DOI: https://dx.doi.org/10.3892/mco.2013.195]
165. Zia-Jahromi, N.; Hejazi, S.H.; Panjepour, M.; Parivar, K.; Gharagozloo, M. Comparison of nucleostemin gene expression in CD133+ and CD133− cell population in colon cancer cell line HT29. J. Cancer Res. Ther.; 2014; 10, pp. 68-72. [DOI: https://dx.doi.org/10.4103/0973-1482.131375]
166. Ding, D.-C.; Liu, H.-W.; Chang, Y.-H.; Chu, T.-Y. Expression of CD133 in endometrial cancer cells and its implications. J. Cancer; 2017; 8, pp. 2142-2153. [DOI: https://dx.doi.org/10.7150/jca.18869]
167. Ding, J.; Xu, W.; Tan, J.; Liu, Z.; Huang, G.; Wang, S.; He, Z. Fluorescence detection of cancer stem cell markers using a sensitive nano-aptamer sensor. Front. Chem.; 2022; 10, 920123. [DOI: https://dx.doi.org/10.3389/fchem.2022.920123]
168. Pang, L.; Huang, X.; Zhu, L.; Xiao, H.; Li, M.; Guan, H.; Gao, J.; Jin, H. Targeted killing of CD133+ lung cancer stem cells using paclitaxel-loaded PLGA-PEG nanoparticles with CD133 aptamers. Nan Fang Yi Ke Da Xue Xue Bao; 2022; 42, pp. 26-35. [DOI: https://dx.doi.org/10.12122/j.issn.1673-4254.2022.01.03]
169. Zahiri, M.; Babaei, M.; Abnous, K.; Taghdisi, S.M.; Ramezani, M.; Alibolandi, M. Hybrid nanoreservoirs based on dextran-capped dendritic mesoporous silica nanoparticles for CD133-targeted drug delivery. J. Cell Physiol.; 2020; 235, pp. 1036-1050. [DOI: https://dx.doi.org/10.1002/jcp.29019]
170. Guo, X.; Zhu, X.; Gao, J.; Liu, D.; Dong, C.; Jin, X. PLGA nanoparticles with CD133 aptamers for targeted delivery and sustained release of propranolol to hemangioma. Nanomedicine; 2017; 12, pp. 2611-2624. [DOI: https://dx.doi.org/10.2217/nnm-2017-0130]
171. Alibolandi, M.; Abnous, K.; Anvari, S.; Mohammadi, M.; Ramezani, M.; Taghdisi, S.M. CD133-targeted delivery of self-assembled PEGylated carboxymethylcellulose-SN38 nanoparticles to colorectal cancer. Artif. Cells Nanomed. Biotechnol.; 2018; 46, pp. 1159-1169. [DOI: https://dx.doi.org/10.1080/21691401.2018.1446969]
172. Shen, S.; Lu, H.; Liu, L.; Wang, Y.; Zhang, C.; Yang, W.; Xu, W. Role of CD44 in tumor-initiating cells of salivary gland pleomorphic adenoma: More than a surface biomarker. Oral Dis.; 2020; 26, pp. 547-557. [DOI: https://dx.doi.org/10.1111/odi.13279]
173. Yokozaki, H.; Ito, R.; Nakayama, H.; Kuniyasu, H.; Taniyama, K.; Tahara, E. Expression of CD44 abnormal transcripts in human gastric carcinomas. Cancer Lett.; 1994; 83, pp. 229-234. [DOI: https://dx.doi.org/10.1016/0304-3835(94)90324-7]
174. Kim, H.-S.; Park, Y.-B.; Oh, J.H.; Jeong, J.; Kim, C.J.; Lee, S.H. Expression of CD44 isoforms correlates with the metastatic potential of osteosarcoma. Clin. Orthop. Relat. Res.; 2002; 396, pp. 184-190. [DOI: https://dx.doi.org/10.1097/00003086-200203000-00028]
175. Mooney, K.L.; Choy, W.; Sidhu, S.; Pelargos, P.; Bui, T.T.; Voth, B.; Barnette, N.; Yang, I. The role of CD44 in glioblastoma multiforme. J. Clin. Neurosci.; 2016; 34, pp. 1-5. [DOI: https://dx.doi.org/10.1016/j.jocn.2016.05.012]
176. Thapa, R.; Wilson, G.D. The importance of CD44 as a stem cell biomarker and therapeutic target in cancer. Stem Cells Int.; 2016; 2016, 2087204. [DOI: https://dx.doi.org/10.1155/2016/2087204]
177. He, Y.; Xue, C.; Yu, Y.; Chen, J.; Chen, X.; Ren, F.; Ren, Z.; Cui, G.; Sun, R. CD44 is overexpressed and correlated with tumor progression in gallbladder cancer. Cancer Manag. Res.; 2018; 10, pp. 3857-3865. [DOI: https://dx.doi.org/10.2147/CMAR.S175681]
178. Alshaer, W.; Hillaireau, H.; Vergnaud, J.; Ismail, S.; Fattal, E. Functionalizing liposomes with anti-CD44 aptamer for selective targeting of cancer cells. Bioconjug. Chem.; 2015; 26, pp. 1307-1313. [DOI: https://dx.doi.org/10.1021/bc5004313]
179. Kim, D.-M.; Kim, M.; Park, H.-B.; Kim, K.-S.; Kim, D.-E. Anti-MUC1/CD44 dual-aptamer-conjugated liposomes for cotargeting breast cancer cells and cancer stem cells. ACS Appl. Bio Mater.; 2019; 2, pp. 4622-4633. [DOI: https://dx.doi.org/10.1021/acsabm.9b00705]
180. Gires, O.; Pan, M.; Schinke, H.; Canis, M.; Baeuerle, P.A. Expression and function of epithelial cell adhesion molecule EpCAM: Where are we after 40 years?. Cancer Metastasis Rev.; 2020; 39, pp. 969-987. [DOI: https://dx.doi.org/10.1007/s10555-020-09898-3]
181. Herlyn, M.; Steplewski, Z.; Herlyn, D.; Koprowski, H. Colorectal carcinoma-specific antigen: Detection by means of monoclonal antibodies. Proc. Natl. Acad. Sci. USA; 1979; 76, pp. 1438-1442. [DOI: https://dx.doi.org/10.1073/pnas.76.3.1438]
182. Went, P.; Vasei, M.; Bubendorf, L.; Terracciano, L.; Tornillo, L.; Riede, U.; Kononen, J.; Simon, R.; Sauter, G.; Baeuerle, P.A. Frequent high-level expression of the immunotherapeutic target Ep-CAM in colon, stomach, prostate and lung cancers. Br. J. Cancer; 2006; 94, pp. 128-135. [DOI: https://dx.doi.org/10.1038/sj.bjc.6602924]
183. Keller, L.; Werner, S.; Pantel, K. Biology and clinical relevance of EpCAM. Cell Stress; 2019; 3, pp. 165-180. [DOI: https://dx.doi.org/10.15698/cst2019.06.188]
184. Zhao, Y.; Xu, J.; Le, V.M.; Gong, Q.; Li, S.; Gao, F.; Ni, L.; Liu, J.; Liang, X. EpCAM aptamer-functionalized cationic liposome-based nanoparticles loaded with miR-139-5p for targeted therapy in colorectal cancer. Mol. Pharm.; 2019; 16, pp. 4696-4710. [DOI: https://dx.doi.org/10.1021/acs.molpharmaceut.9b00867]
185. Mashreghi, M.; Zamani, P.; Karimi, M.; Mehrabian, A.; Arabsalmani, M.; Zarqi, J.; Moosavian, S.A.; Jaafari, M.R. Anti-epithelial cell adhesion molecule RNA aptamer-conjugated liposomal doxorubicin as an efficient targeted therapy in mice bearing colon carcinoma tumor model. Biotechnol. Prog.; 2021; 37, e3116. [DOI: https://dx.doi.org/10.1002/btpr.3116]
186. Khezrian, S.; Khoee, S.; Caceres, M. Synthesis of combinatorial janus nanoparticles based on EpCAM-PEG/PCL for targeted therapy of human colorectal adenocarcinoma. J. Biomed. Mater. Res. A; 2020; 108, pp. 2291-2304. [DOI: https://dx.doi.org/10.1002/jbm.a.36986]
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