Introduction
The prevalence of cancer is growing at a fast pace on a global scale. The number of worldwide cases of urologic malignancies, which include cancers of the prostate, bladder, kidney, ureter, and renal pelvis, exceeded two million in 2020. These cases resulted in more than 0.76 million fatalities. The rates of morbidity and death are steadily increasing [1]. Prostate cancer constitutes 27% of all newly diagnosed cancer cases in males, whereas bladder, kidney, and renal pelvis tumors are among the top 10 most often diagnosed malignancies. Kidney (including renal pelvis) cancer ranks as the ninth most prevalent cancer among women. Prostate cancer is the most common malignancy in males in 112 countries and the primary cause of cancer-related mortality in 48 nations [2].
The increasing occurrence and death rates of urologic malignancies emphasize the pressing need for improved therapeutic care, despite the use of effective treatment strategies involving various combinations of surgery, radiation, and systemic medicines. The majority of initial prostate tumors express the androgen receptor (AR). For many decades, the mainstay of therapy for prostate cancer has been the use of several types of endocrine treatments to inhibit the effects of androgens [3]. Recent studies suggest that men with intermediate risk of low-volume metastatic prostate cancer may benefit from treatment strategies involving various combinations of surgery, radiation, and systemic treatments. However, the administration of chemotherapeutic medicines such as docetaxel and doxorubicin often results in treatment resistance and significant side effects. Androgen deprivation therapy may have a negative effect on skeletal metabolism. As a result, there is an urgent need to investigate novel drugs that might successfully treat prostate cancer with few adverse effects [4, 5]. Nonmuscle-invasive bladder cancer (NMIBC) is identified in approximately 70% of patients diagnosed with bladder cancer; the remaining cases involve advanced bladder cancer and muscle-invasive bladder cancer (MIBC). Presently, the prevailing approach for managing NMIBC involves performing transurethral resection of bladder cancer (TURBT), followed by intravesical therapy to impede its progression to a more advanced stage or prevent recurrence. To increase the survival time of patients diagnosed with MIBC and advanced-stage bladder tumors, systemic and intraperitoneal chemotherapy, adjuvant radiotherapy, photodynamic therapy, and targeted medications are frequently used in clinical practice. Nevertheless, despite completing the entire course of standard therapy and enduring all associated side effects, bladder cancer patients continue to experience an unsatisfactory recurrence rate. Recurrence or progression occurs in 40% of NMIBC patients with BCG instillation and in 44% of patients despite the administration of chemotherapy instillation following TURBT [6–8]. In addition, there is a substantial recurrence rate of as much as 40% following surgical resection of kidney cancer [9, 10]. Diverse novel therapeutic modalities, such as targeted therapy and immunotherapy, have been identified and clinically implemented over the past several decades to improve therapeutic outcomes for patients. However, these therapies have certain limitations, such as the intricate characteristics of the molecular targets and the occurrence of severe adverse effects [11]. The management of drug delivery and response in tumor regions continues to present difficulties as a result of the complexity and heterogeneity of the tumor microenvironment. Thus, nanoscale antitumor drugs are necessary.
Nanomedicine is a developing technology used for managing cancer. Nanomedicine, which refers to interventions involving substances measuring 1–1000 nm, represents a nanosized system with distinctive physical and chemical features, such as small size with large surface area and the ability to manifest quantum effects [12, 13]. Nanomedicine is defined as the application of nanotechnology for medical purposes. This involves the design and use of nanomaterials and nanodevices to improve the pharmacological properties, drug delivery, diagnostics, and treatment of diseases [14, 15].
Nanocarriers are specialized vehicles capable of efficiently traversing various biological barriers and targeting tumor cells via both passive and aggressive methods, leveraging their exceptional selectivity [16]. Nanomedicine may enhance the efficacy of conventional antitumor medications while reducing their negative effects [17]. Moreover, nanoparticles (NPs) can transport several therapeutic drugs simultaneously to provide synergistic effects [18]. They may also be adjusted to have prolonged or brief circulation periods by precisely managing their dimensions and surface characteristics [19]. Additionally, they may overcome resistance to several drugs and reduce the negative effects associated with cancer treatment [20].
Compared with nanocarriers, microsized drug carriers are larger, generally measuring greater than 1 µm. The smaller size of nanocarriers allows for unique interactions with biological tissues at the cellular and molecular levels [21]. Nanocarriers have a relatively high surface area-to-volume ratio, increasing their drug loading capacity and interaction with target cells. This property also improves their ability to penetrate biological barriers such as the blood‒brain barrier [22]. Compared with microsized drug carriers, the small size and modifiable surface properties of nanocarriers facilitate the attachment of targeting ligands, enabling site-specific delivery and improved therapeutic outcomes [23].
In 2007, studies demonstrated the feasibility of using nanoparticles for thermotherapy in patients with prostate cancer [24]. This method may generate hyperthermic and thermoablative temperatures in the prostate on the basis of the intensity of the magnetic field used. The nanoparticles were not evenly distributed throughout the prostate in this first trial. An assessment of the safety and effectiveness of nanoparticle albumin-bound paclitaxel for treating nonmuscle invasive bladder cancer that is resistant to treatment was conducted [25]. It was confirmed that a 2-methoxyestradiol nanocrystal colloidal dispersion is effective against metastatic renal cell carcinoma [26] and refractory, castration-resistant prostate cancer [27]. Consistently, fresh and compelling evidence continues to substantiate the therapeutic efficacy of nanomaterials in the treatment of malignancies in the urinary system.
Research in the domain of nanomedicine in urologic cancer has experienced substantial expansion, as evidenced by the publication of a considerable number of articles each year. It is imperative for researchers to develop expertise in comprehending research trends and conscientiously monitor the most noteworthy recent developments, notwithstanding the challenges these may present. Therefore, it is imperative to undertake a comprehensive and quantifiable analysis that identifies present areas of interest and suggests directions for future research. To promptly determine the development and future potential of a specific scientific field, it is critical to conduct a comprehensive review of the published literature. Bibliometric analysis is a suitable methodology for conducting an exhaustive investigation of an entire body of work of academic subject matter, which includes a substantial quantity of publications [28]. It may be necessary to conduct several iterations (analysis, data purification, and reanalysis) prior to applying the generated clustering for the purpose of assessing the research topic. A bibliometric analysis of nanomedicine in urologic malignancies is not currently available.
The current bibliometric analysis included all articles published from January 1, 2001, to December 29, 2023, that were specifically pertinent to the application of nanomedicine in the treatment of urologic cancer. The objective of this study was to provide a comprehensive synopsis of this discipline, including noteworthy advancements, the prevailing patterns in research, and the topics that have become the focus of recent research. On the basis of this study, researchers can identify not only noteworthy publications, journals, and potential collaborators but also future research directions.
Methods
Data sources and search strategies
We use the Science Citation Index Expanded (SCI-Expanded) from the Web of Science Core Collection (WoSCC) from Clarivate Analytics as our primary data source. The WoSCC is a widely used database for bibliometric research that includes articles from almost 9000 high-impact journals.
The search was performed on December 29th, 2023, and specifically focused on papers related to the use of nanomedicine in the treatment of urologic cancer. The search query was formulated as follows: topic = “nanomaterial OR nanoparticle OR nanomedicine OR nanostructure OR nanobiomaterial OR nanocrystal OR nanodot OR nanorod” AND “(renal OR kidney OR bladder OR urothelial OR ureteral OR ureter OR pelvic OR prostatic OR prostate) NEAR/5 (cancer OR tumor OR oncology OR neoplasm OR carcinoma)” AND “publication date = (January 1, 2001–December 29, 2023)”. The publication date should be within the range of January 1, 2001, to December 29, 2023. The data, including the yearly research numbers, nations, institutions, authors, journals, citations, and keywords, were independently extracted by two writers, Xiaopeng Lan and Mei Feng. A third reviewer was consulted to resolve any discrepancies between the two initial reviewers. The downloaded search results are shown in both plain text and BibTex formats, notably in the area labeled "Full Records and Cited References". Furthermore, the range of publications was limited to reviews and primary research papers, and only the English language was used.
Data extraction and analysis
To ensure the accuracy of the data and the reliability of the study, two researchers independently collected and analyzed the data. Coauthorship, co-occurrence, and cocitation analysis are the fundamental and paramount indicators in bibliometric analysis. Coauthorship analysis is conducted to investigate the connections among authors, nations, or organizations. Co-occurrence analysis is a quantitative method used to analyze the most often occurring elements in publications. A cocitation analysis was conducted by comparing the ranking results with the cocitation scores.
The process of visualizing bibliometric analysis was carried out using R language software (version 4.2.3), CiteSpace (version 6.2. R4), and VOSviewer (version 1.6.20). The variables in this descriptive research were quantified using numerical values and are expressed as percentages. P values were not calculated due to the lack of comparisons.
The bibliometrix R tool was used to extract data on keywords, countries, and years. Afterwards, heatmaps were created to visually represent the frequency of publications over the whole country over a period of time. In addition, this research leverages VOSviewer, a bibliometric tool that applies distance-based methodologies to visually represent bibliometric networks. VOSviewer is specifically used to study and display networks of cooperation across nations, institutions, journals, and authors. Additionally, it is used to perform keyword overlay analysis. The configuration parameters for VOSviewer were set as follows: The counting technique used was the comprehensive counting strategy. Nevertheless, papers that include a substantial number of states, entities, or writers are disregarded. Each category in a document has a maximum limit of 25. CiteSpace was used to depict keyword co-occurrence, clustering, and bursts due to its capacity to dynamically present evolving bibliometric networks. The following are the parameters for CiteSpace: the link retention factor is set to 2, the lookback years are set to − 1, and the e value for the top N is set to 2. The time period is from 2001 to 2023, with each slice representing a span of 1 year. The selection criterion was the top 50.
This bibliometric analysis did not include patient consent or clinical investigations. Consequently, the presence of institutional review boards and ethical committees was superfluous.
Results
Analysis of annual publication and citation trends
The number of studies on nanomedicine in urologic cancers has steadily increased over the years due to advancements in nanomedicine-related technologies. As shown in our flowchart, the retrieval process produced an initial count of 2505 documents. This encompasses many forms of literature, such as meeting abstracts, editorial articles, proceedings papers, book chapters, and other similar categories. Of the remaining articles, 2386 were written in English. A total of 1949 publications and 437 review articles were included, as shown in Fig. 1. The annual publishing volume is a quantitative metric that reflects the degree of academic interest in a specific subject. The bar chart in Fig. 2A shows that a total of 2386 articles covering the period from 2001 to 2023 met the inclusion criteria. Over the past 23 years, there has been a consistent increase in the number of publications, indicating a growing interest in this subject among professionals. Additionally, to assess the relationship between the quantity of publications and the year of publication, the blue curve in Fig. 2A serves as a representation of the generalized additive model. The findings showed that the model closely matched the yearly distribution pattern of the literature, with a high level of compliance (R2 = 0.99931). It is evident from the trajectory of the curve that the quantity of pertinent research publications has experienced substantial and rapid growth since 2014. However, starting in 2018, the pattern of the number of published articles reached a state of equilibrium, and the yearly count of articles began to stabilize. Furthermore, the projected curve clearly demonstrates the yearly growth in publishing volume and the expected continuation of this increasing trend in the future.
Fig. 1 [Images not available. See PDF.]
Flow chart of the present study
Fig. 2 [Images not available. See PDF.]
A Global trends in the publication of nanomedicine in urologic cancer. The blue curve shows the annual publication growth trend. The equation y = 225.44857/(1 + exp(− 0.35978*(x-2012.95534))), R2 = 0.99931, can be used to predict the number of annual documents. B The dynamic attributes of publications in the ten leading countries between 2001 and 2023. C Network mapping of international collaboration based on 2386 papers. D Network mapping of cooperation among the top 100 articles
Analysis of productive countries/regions
The study included publications from 462 organizations across 90 nations. The United States had the highest number of published documents, accounting for approximately 31.01% of the total (Table 1). Additional nations with a substantial number of articles include the People's Republic of China, India, South Korea, and Iran. The United States has the largest total number of citations, reaching 57,579, which significantly surpasses that of other nations. Literature publications from China, South Korea, and Germany are frequently cited. The United States ranks first in terms of the number of citations per manuscript, followed by Germany. By analyzing the data on publications from the top 10 nations over the past 14 years, we can determine the annual number of papers published in various countries. The United States and the People's Republic of China consistently have the highest number of articles each year. Prior to 2018, the United States had a considerably higher publication rate of articles than China did. However, starting in 2018, China surpassed the United States and became the leading producer of articles on an annual basis (Fig. 2B).
Table 1. Top 10 most productive countries/regions associated with nanomedicine in urologic cancer
Rank | Country/Region | Publications | Percentage | Total citations | Average article citation | Total link strength |
---|---|---|---|---|---|---|
1 | USA | 740 | 31.01 | 57,579 | 77.81 | 134,894 |
2 | People R China | 536 | 22.46 | 19,435 | 36.26 | 86,148 |
3 | India | 120 | 5.03 | 3798 | 31.65 | 32,499 |
4 | South Korea | 113 | 4.74 | 7901 | 69.92 | 31,454 |
5 | Iran | 92 | 3.86 | 2076 | 22.57 | 29,939 |
6 | Germany | 87 | 3.65 | 6385 | 73.39 | 26,070 |
7 | Canada | 83 | 3.48 | 3523 | 42.45 | 22,793 |
8 | Italy | 68 | 2.85 | 3156 | 46.41 | 23,446 |
9 | England | 63 | 2.64 | 3468 | 55.05 | 16,578 |
10 | France | 57 | 2.39 | 3555 | 62.37 | 18,297 |
Collaboration among countries
As shown in the chordal graph (Fig. 2C), the United States formed partnerships with the majority of countries and regions. Figure 3A shows a network diagram created by VOSviewer to show the cooperative relationships between 35 countries that have published more than 10 articles. The thickness of the lines represents the level of international collaboration, referred to as total link strength (TLS). The United States, the People's Republic of China, India, South Korea, and Iran were the five leading countries in terms of TLS (Table 1). The network visualization map (Fig. 3B) depicts the collaborative relationships and average publication years of different nations and regions. The network visualization map (Fig. 3C) displays the collaboration links, as well as the average publication year, across the nations and regions of the top 100 articles. Among the top 100 articles on nanomedicine in urologic malignancies, international cooperation was the most common, as shown in Fig. 2D.
Fig. 3 [Images not available. See PDF.]
A Correlations among the countries/regions with more than 10 articles. VOSviewer was responsible for creating the graph. The line thickness indicates the citation strength. B Network visualization map of collaboration relationships and average publication years of the various countries and regions. C Network visualization map of cooperation connections and average publication years of the nations and regions of the top 100 publications. D Network visualization map of collaboration relationships of institutions with at least 10 papers. E Network visualization map of collaboration relationships of institutions with at least 3 papers. F Network visualization map of cooperation connections and average publication years of the institutions with more than 15 publications
Contribution of productive institutions
Table 2 shows that five of the top ten most productive institutions for nanomedicine for urologic malignancies are based in the United States. The Chinese Academy of Sciences (CAS) is the leading institution in this discipline, with 2.35% of all published articles. The articles from MIT and Harvard University obtained the highest number of citations. Given that the quality of publications may be more precisely measured by the number of citations per paper, papers from MIT and Harvard University display greater quality, as evidenced by counts of 347.04 and 210.84 citations per manuscript, respectively. The network visualization maps (Fig. 3D, E) revealed collaborative links among different universities that had published a minimum of 10 publications or at least 3 papers. The network visualization map (Fig. 3F) displays the collaboration links and the mean publication years of institutions that published more than 15 articles. The CAS and Harvard Medical School were the leading institutions in terms of TLS (Table 2).
Table 2. Top 10 most productive institutions associated with nanomedicine in urologic cancer
Rank | Institution | Country | Publications | Percentage | Citations | Citations per paper | Total link strength |
---|---|---|---|---|---|---|---|
1 | Chinese Acad Sci | China | 56 | 2.35 | 3001 | 53.59 | 88 |
2 | Harvard Univ | USA | 44 | 1.84 | 9277 | 210.84 | 68 |
3 | Sun Yat Sen Univ | China | 32 | 1.34 | 1028 | 32.13 | 25 |
4 | Harvard Med Sch | USA | 30 | 1.26 | 1445 | 48.17 | 86 |
5 | Johns Hopkins Univ | USA | 28 | 1.17 | 1704 | 60.86 | 33 |
6 | MIT | USA | 27 | 1.13 | 9370 | 347.04 | 58 |
7 | Shanghai Jiao Tong Univ | China | 26 | 1.09 | 737 | 28.35 | 34 |
8 | Univ Texas MD Anderson Canc Ctr | USA | 25 | 1.05 | 1361 | 54.44 | 40 |
9 | Univ Toronto | Canada | 25 | 1.05 | 1126 | 45.04 | 29 |
10 | Jilin Univ | China | 24 | 1.01 | 907 | 37.79 | 26 |
Analysis of authors
A total of thousands of researchers have authored 2386 publications on nanomedicine in urologic cancer. A total of 106 writers have written over 5 publications each. Farokhzad Omid C emerged as the most prolific author in this domain, having published 21 articles and receiving the greatest number of citations, totaling 6271 for his works (Table 3). In addition, Langer R, Ivkov R, Rege K, and Ossolinski K were among the five most productive authors during the past 23 years. Remarkably, Langer R. was the second most often mentioned author, despite having produced only 13 works on this particular topic. He has the highest citation rate per piece. The United States leads in this field of research, as shown by the presence of 5 American authors in the top 10. The collaboration networks and grouping patterns of authors who published more than 10 or 2 publications were analyzed (Fig. 4A, B). Figure 4C illustrates the cooperation among the authors who are mentioned together.
Table 3. Top 10 most productive authors related to nanomedicine in urologic cancer
Rank | Author | Country | Publications | Citations | Citations per paper | H-Index | Total link strength |
---|---|---|---|---|---|---|---|
1 | Farokhzad, Omid C | USA | 21 | 6271 | 298.62 | 109 | 6517 |
2 | Langer, Robert | USA | 13 | 4690 | 360.77 | 52 | 4334 |
3 | Ivkov, Robert | USA | 12 | 690 | 57.50 | 34 | 2666 |
4 | Rege, Kaushal | USA | 12 | 623 | 51.92 | 25 | 701 |
5 | Ossolinski, Krzysztof | Poland | 11 | 125 | 11.36 | 10 | 5466 |
6 | Ruman, Tomasz | Poland | 11 | 125 | 11.36 | 27 | 5466 |
7 | Zheng, Gang | China | 11 | 621 | 56.45 | 36 | 1314 |
8 | Chen, Wei | China | 10 | 737 | 73.70 | 41 | 607 |
9 | Niziol, Joanna | Poland | 10 | 121 | 12.10 | 14 | 5036 |
10 | Pomper, Martin G | USA | 10 | 287 | 28.70 | 78 | 1085 |
Fig. 4 [Images not available. See PDF.]
A Visualization map of cocited authors with more than 10 papers generated by VOSviewer. B Visualization map of cocited authors with more than 2 papers generated by VOSviewer. C Visualization map of cocited authors generated by VOSviewer
Analysis of the top articles
To determine the top 100 papers, we ranked the articles on the basis of the number of times they were cited (Supplementary Table S1). The top 100 papers received a total of 43,413 citations. The median number of citations for these top papers was 290.5 (ranging from 187 to 4013). The ten articles with the highest number of citations were published in 2018 or earlier (Table 4). The paper titled "In vivo cancer targeting and imaging with semiconductor quantum dots," written by Chung, LWK et al. in 2004, received the greatest number of citations (4013). The paper titled "Current knowledge on exosome biogenesis and release," written by Llorente, Alicia et al. in 2018, had the highest average annual citation count (209.71) and the second-highest total number of citations (1468).
Table 4. The 10 most cited papers on nanomedicine in urologic cancer from 2001 to 2023
Rank | Title | Corresponding author | Journal | Year | Total citations | Average citations per Year |
---|---|---|---|---|---|---|
1 | In vivo cancer targeting and imaging with semiconductor quantum dots | Chung, LWK | Nature Biotechnology | 2004 | 4013 | 191.1 |
2 | Current knowledge on exosome biogenesis and release | Llorente, Alicia | Cellular and Molecular Life Sciences | 2018 | 1468 | 209.71 |
3 | Targeted nanoparticle-aptamer bioconjugates for cancer chemotherapy in vivo | Farokhzad, OC | Proceedings of the National Academy of Sciences of the United States of America | 2006 | 1442 | 75.89 |
4 | Active targeting schemes for nanoparticle systems in cancer therapeutics | Brannon-Peppas, Lisa | Advanced Drug Delivery Reviews | 2008 | 1333 | 78.41 |
5 | Formulation of functionalized PLGA-PEG nanoparticles for in vivo targeted drug delivery | Farokhzad, OC | Biomaterials | 2007 | 1053 | 58.5 |
6 | Liposomes and nanoparticles: nanosized vehicles for drug delivery in cancer | Seifalian, AM | Trends in Pharmacological Sciences | 2009 | 958 | 59.88 |
7 | Preclinical Development and Clinical Translation of a PSMA-Targeted Docetaxel Nanoparticle with a Differentiated Pharmacological Profile | Farokhzad, OC | Science Translational Medicine | 2012 | 906 | 69.69 |
8 | Nanotechnology applications in cancer | Nie, Shuming | Annual Review of Biomedical Engineering | 2007 | 844 | 46.89 |
9 | Targeted delivery of cisplatin to prostate cancer cells by aptamer functionalized Pt(IV) prodrug-PLGA-PEG nanoparticles | Lippard, SJ | Proceedings of the National Academy of Sciences of the United States of America | 2008 | 822 | 48.35 |
10 | Quantum dot—Aptamer conjugates for synchronous cancer imaging, therapy, and sensing of drug delivery based on Bifluorescence resonance energy transfer | Jon, Sangyong | Nano Letters | 2007 | 806 | 44.78 |
Analysis of keywords
By analyzing keyword cooccurrences in many published studies, we can classify high-frequency keywords and evaluate the strength of relationships between terms, revealing an academic subject's research limits and internal structure. Table 5 shows the top 10 terms, together with their frequencies, centrality, and first-occurrence timings. A network visualization map was used to display the keywords' cooperative connections (Fig. 5A). The most popular search phrases were "prostate cancer," "drug delivery," "nanoparticles," "therapy," "gold nanoparticles," "cells," "cancer," and "expression." The most recent term in the top ten was "gold nanoparticles." Keywords that occurred more than 15 times were subjected to cooperation and citation network analysis (Fig. 5B). Keyword co-occurrence and citation network analyses were conducted on 100 recently published articles in famous journals (Fig. 5C). We employed cluster analysis to categorize the data by similarity via keyword co-occurrence networks to obtain a better grasp of the field's core knowledge structure. As a consequence, we were able to create 15 keyword clusters (Fig. 5D) in the field of nanomedicine in urologic cancer. The weighted mean silhouette S of the 15 clusters is 0.9077, suggesting that the clustering findings are of high quality and that the members of the clusters are quite homogeneous. CiteSpace was utilized to identify burst keywords on the basis of research hotspots. The burst map may demonstrate how keywords have steadily grown over time, allowing one to judge the period's degree of attention and research direction. Research on cancer, contrast agents, gene delivery, and malignancies was conducted from 2004 to 2017 (Fig. 6A). However, since 2019, mechanisms, exosomes, nanoparticles, biomarkers, mesoporous silica nanoparticles, extracellular vesicles, efficacy, and androgen receptors have received significant attention as potential future research frontiers and trends in the field of nanomedicine in urologic cancer.
Table 5. High-frequency keywords
Rank | Keyword | Frequency | Centrality | Year of first appearance |
---|---|---|---|---|
1 | Prostate cancer | 541 | 0.19 | 2005 |
2 | Drug delivery | 264 | 0.45 | 2006 |
3 | Prostate-cancer | 253 | 0.3 | 2002 |
4 | Nanoparticles | 239 | 0.03 | 2004 |
5 | Delivery | 228 | 0.14 | 2004 |
6 | Therapy | 209 | 0.03 | 2002 |
7 | Gold nanoparticles | 190 | 0 | 2008 |
8 | Cells | 168 | 0.07 | 2004 |
9 | Cancer | 144 | 0.27 | 2004 |
10 | Expression | 144 | 0.41 | 2002 |
Fig. 5 [Images not available. See PDF.]
A Network visualization map of the cooperation connections of the keywords. B Network visualization map of the cooperation connections of keywords that appeared more than 15 times. C Network visualization map of the cooperation connections of the keywords from the 100 recently published papers. D Clusters of keywords: All nodes contained within a color block are members of the cluster, which is represented by a color block. The cluster scale decreases as the number of clusters increases
Fig. 6 [Images not available. See PDF.]
A The top 25 keywords with the strongest citation bursts based on CiteSpace. The horizontal red stripes indicate the years in which the keyword was utilized most frequently. The horizontal green stripes indicate the years in which the keyword was utilized least frequently. B Visualization map of the top 25 references with the strongest citation bursts generated by CiteSpace. C Cocited reference collaboration network visualized by VOSviewer
Analysis of research trends
Figure 7A presents a historical view of the variability of co-cited terms related to nanomedicine in the context of urologic cancer. A total of fifteen clusters were generated on the basis of the provided keywords. Figure 7B presents a sequential view of the changes in co-cited references over time. The references were divided into eight groups. The research hotspots are represented by themes with large yellow nodes, indicating a significant number of recent articles. Figure 6B displays the burst map representing the top 25 references. We used VOSviewer to analyze the co-cited references. The co-cited cooperation network, which includes references referenced more than 80 times, is shown in Fig. 6C.
Fig. 7 [Images not available. See PDF.]
A The timeline view for cocited keywords. The magnitude of the node corresponds to the citation count of the reference. The cocitation relationships are indicated by the curves connecting the nodes. B The timeline view for cocited references. The node size represents the number of citations of the reference
Discussion
The increasing prevalence of nanomedicine in the treatment of urologic cancer has been attributed to ongoing progress in the field of materials science. From 2009 to 2017, there was a substantial surge in the number of pertinent articles, which increased at an exponential rate from 36 to 217. Despite the yearly allocation of more research opportunities toward nanomedicine, the annual volume of literature in this domain has plateaued in recent years. Over the past two decades, the United States has consistently produced the highest quantity of articles as a result of its research institutions and scholars. Additionally, the robust national economies and substantial investments in medical research in Asian and European nations have contributed to their significance. Five of the top ten article-publishing institutions are located in the United States, with the remaining four being in China. These high-producing nations, as illustrated in Fig. 3A–C, assign significant value to international cooperation. Several nations, including the United States, China, India, and South Korea, were early advocates of international cooperation. The literature originating from the United States, Germany, South Korea, and France has a greater mean number of citations per paper (Table 1). As a result, many latecomers are provided with valuable research references. The Chinese Academy of Sciences, situated in China, produced 56 articles in total. However, the publication volumes of the top ten publishing institutions are essentially identical. MIT was identified as the most-cited institution, with an average of 347.04 citations per article. Harvard University ranked second with 210.84 citations per article. The United States is home to five of the ten most prolific authors, whereas Poland and China contribute the remaining three and two, respectively. Farokhzad, an American author, is the most prolific and has the highest H-index. As illustrated in Fig. 7B, "quantum dots" and "gene delivery" comprised the most robust clusters prior to 2013. "Bladder cancer" has emerged as the most prominent keyword cluster since 2017, directing our attention toward the most recent and potentially most auspicious domains of study.
The understanding of nanomedicine in urologic cancer has advanced significantly with the discovery of the increased permeability and retention (EPR) effect, which enables nanomedicines to enter and accumulate in tumors because of leaky blood arteries and inadequate lymphatic drainage. Two forms of passively targeted nanoparticles authorized for clinical usage are lipid-based nanomedicines and nanoparticle albumin-bound nanomedicines. Nanomedicines, such as liposomes composed of phospholipids and glycerides, include PEGylated liposomal doxorubicin [29]. This formulation extends the half-life of doxorubicin and decreases its toxicity [30]. The combination of nanoparticles with albumin reduces toxicity and enhances the pharmacokinetics of the nanodrug [31]. In 2002, McMenemin, Harris, and Fossa initiated three phase II clinical studies to study the effectiveness of lipid or PEGylated doxorubicin in treating mCRPC. Camptothecin, dexamethasone, and rapamycin encapsulated in various liposomal formulations have been used in clinical trials involving patients with prostate cancer [32–34]. The first relevant clinical trial on bladder tumors was published in 2003 by Winquist et al., who focused on the use of PEGylated doxorubicin for treating advanced MIBC (unresectable) [35]. Sridha conducted a phase II clinical study to compare the therapeutic efficacy of paclitaxel in a nanoparticle-albumin-bound form with that of the traditional formulation in metastatic urothelial cancer [36]. In 2017, Voss conducted a phase II clinical trial on the effectiveness of the polymer camptothecin in treating metastatic renal cell cancer [37].
Numerous nanomedicines may specifically target tumor cells via unique architectures or ligands. Kim and colleagues placed Toll-like receptor (TLR) 7/8 agonists inside poly(lactic-co-glycolic acid) (PLGA) nanoparticles under the skin to help activate and grow dendritic cells [38]. The nanoparticles increased the number of antigen-specific CD8 + T cells and strengthened the cytotoxic T lymphocyte (CTL) response. These nanoparticles demonstrated superior therapeutic efficacy compared with the standard formulation in the prevention and treatment of melanoma, bladder cancer, and RCC. To test how immunotherapy works in primary or metastatic RCC, a tumor vaccine was made with a DNA sensor (AIM2), a tumor antigen (CAIX), and a delivery system based on folic acid-grafted PEI600-CyD (H1) nanoparticles [39]. Zhu et al. combined PLZ4 nanoparticles that target bladder cancer with photodynamic therapy (PDT) to create reactive oxygen species (ROS) and started protein carbonylation and dendritic cell maturation in xenografts of mice that developed bladder cancer on their own [40]. Guo et al. used core–shell nanoparticles modified with prostate-specific membrane antigen aptamer (Apt) against paclitaxel (PTX)-resistant LNCaP (LNCaP/PTX) cells. The nanoparticles prevented epithelial–mesenchymal transition (EMT) and increased the responsiveness of cancer cells to PTX [41].
Bibliometric analysis is a methodical and impartial methodology used to monitor the progress of research on a certain topic and provides a valuable resource for future academics [42]. This paper presents an in-depth analysis of the latest studies on nanomedicine in the treatment of urologic cancer over the last twenty years. Novices in this discipline may use this article to understand the present status of study in this area and decide on the most appropriate course of action before initiating fresh inquiries. This study has several limitations. It might not have covered all articles published before this article.
Conclusion
This is the first bibliometric examination of the literature on nanomedicine in urologic cancer. We analyzed data on countries/regions, institutions, authors, cited articles, keywords, and other relevant information. We found that the quantity of articles in this category increased consistently over time. American writers and organizations have made the greatest contributions to this topic. Simultaneously, the most recent areas of study interest have been discovered. We anticipate that this study will be beneficial to other researchers in the field.
Acknowledgements
We would like to thank the anonymous reviewers for their helpful remarks.
Author contributions
Conceptualization, Luchen Zhang; Data curation, Luchen Zhang and Jilu Zheng; Formal analysis, Mei Feng; Funding acquisition, Chunlei Liu; Investigation, Xiaopeng Lan; Methodology, Mei Feng, Luchen Zhang and Yizhen Wang; Project administration, Ranlu Liu; Resources, Mei Feng; Software, Xiaopeng Lan and Lili Chen; Supervision, Xiaoyan Wang and Ranlu Liu; Validation, Lili Chen and Chao Han; Visualization, Yizhen Wang, Xiaoyan Wang, Chunlei Liu and Ranlu Liu; Writing—original draft, Xiaopeng Lan; Writing—review and editing, Lili Chen, Chao Han and Jilu Zheng.
Funding
No funding was available for this study.
Data availability
Data is provided within the manuscript or supplementary information files.
Declarations
Ethics approval and consent to participate
The content of this article has no ethical implications.
Consent for publication
All authors have read and approved the final manuscript and agree with its submission to the Journal of Translational Medicine.
Competing interests
The authors declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Publisher's Note
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References
1. Sung, H; Ferlay, J; Siegel, RL et al. Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin; 2021; 71,
2. Siegel, RL; Miller, KD; Wagle, NS; Jemal, A. Cancer statistics, 2023. CA Cancer J Clin; 2023; 73,
3. Poutanen, M; Hagberg Thulin, M; Härkönen, P. Targeting sex steroid biosynthesis for breast and prostate cancer therapy. Nat Rev Cancer; 2023; [DOI: https://dx.doi.org/10.1038/s41568-023-00609-y] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/37684402]
4. Sandhu, S; Moore, CM; Chiong, E; Beltran, H; Bristow, RG; Williams, SG. Prostate cancer. Lancet; 2021; 398,
5. Elbagory, AM; Hull, R; Meyer, M; Dlamini, Z. Reports of plant-derived nanoparticles for prostate cancer therapy. Plants (Basel); 2023; 12,
6. Flaig, TW; Spiess, PE; Agarwal, N et al. Bladder cancer, Version 3.2020, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw; 2020; 18,
7. Mertens, LS; van der Heijden, MS. Accelerating neoadjuvant chemotherapy for muscle-invasive bladder cancer. Lancet Oncol; 2024; 25,
8. Meeks, JJ; Black, PC; Galsky, M et al. Checkpoint inhibitors in urothelial carcinoma-future directions and biomarker selection. Eur Urol; 2023; 84,
9. Wu, R; Wang, K; Gai, Y et al. Nanomedicine for renal cell carcinoma: imaging, treatment and beyond. J Nanobiotechnol; 2023; 21,
10. Martini, A; Turri, F; Barod, R et al. Salvage robot-assisted renal surgery for local recurrence after surgical resection or renal mass ablation: classification, techniques, and clinical outcomes. Eur Urol; 2021; 80,
11. Bolek, H; Ürün, Y. Adjuvant therapy for renal cell carcinoma: a systematic review of current landscape and future directions. Crit Rev Oncol Hematol; 2023; 192, [DOI: https://dx.doi.org/10.1016/j.critrevonc.2023.104144] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/37748694]
12. de Lázaro, I; Mooney, DJ. Obstacles and opportunities in a forward vision for cancer nanomedicine. Nat Mater; 2021; 20,
13. Wang, L; Yang, D; Lv, JY; Yu, D; Xin, SJ. Application of carbon nanoparticles in lymph node dissection and parathyroid protection during thyroid cancer surgeries: a systematic review and meta-analysis. Onco Targets Ther; 2017; 10, pp. 1247-1260.[COI: 1:CAS:528:DC%2BC1cXhsFamurrM] [DOI: https://dx.doi.org/10.2147/OTT.S131012] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/28280359][PubMedCentral: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5338936]
14. Zhou, Z; Vázquez-González, M; Willner, I. Stimuli-responsive metal-organic framework nanoparticles for controlled drug delivery and medical applications. Chem Soc Rev; 2021; 50,
15. Mujahid, MH; Upadhyay, TK; Khan, F et al. Metallic and metal oxide-derived nanohybrid as a tool for biomedical applications. Biomed Pharmacother; 2022; 155,[COI: 1:CAS:528:DC%2BB38Xis1Cis7rM] [DOI: https://dx.doi.org/10.1016/j.biopha.2022.113791] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/36271568]
16. Li, X; Chen, L; Luan, S et al. The development and progress of nanomedicine for esophageal cancer diagnosis and treatment. Semin Cancer Biol; 2022; 86,
17. Kong, C; Zhang, S; Lei, Q; Wu, S. State-of-the-art advances of nanomedicine for diagnosis and treatment of bladder cancer. Biosensors (Basel); 2022; 12,
18. Jeannot, V; Gauche, C; Mazzaferro, S et al. Anti-tumor efficacy of hyaluronan-based nanoparticles for the codelivery of drugs in lung cancer. J Control Release; 2018; 275, pp. 117-128.[COI: 1:CAS:528:DC%2BC1cXjt12qu7g%3D] [DOI: https://dx.doi.org/10.1016/j.jconrel.2018.02.024] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/29474960]
19. Zhang, SQ; Fu, Q; Zhang, YJ et al. Surface loading of nanoparticles on engineered or natural erythrocytes for prolonged circulation time: strategies and applications. Acta Pharmacol Sin; 2021; 42,
20. Gote, V; Nookala, AR; Bolla, PK; Pal, D. Drug resistance in metastatic breast cancer: tumor targeted nanomedicine to the rescue. Int J Mol Sci; 2021; 22,
21. Liu, Q; Zhang, X; Xue, J et al. Exploring the intrinsic micro-/nanoparticle size on their in vivo fate after lung delivery. J Control Release; 2022; 347, pp. 435-448.[COI: 1:CAS:528:DC%2BB38Xhtlart7fF] [DOI: https://dx.doi.org/10.1016/j.jconrel.2022.05.006] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/35537539]
22. Kazsoki, A; Szabó, P; Domján, A et al. Microstructural distinction of electrospun nanofibrous drug delivery systems formulated with different excipients. Mol Pharm; 2018; 15,
23. Sahoo, RK; Gupta, T; Batheja, S et al. Surface engineered dendrimers: a potential nanocarrier for the effective management of glioblastoma multiforme. Curr Drug Metab; 2022; 23,
24. Johannsen, M; Gneveckow, U; Thiesen, B et al. Thermotherapy of prostate cancer using magnetic nanoparticles: feasibility, imaging, and three-dimensional temperature distribution. Eur Urol; 2007; 52,
25. McKiernan, JM; Barlow, LJ; Laudano, MA; Mann, MJ; Petrylak, DP; Benson, MC. A phase I trial of intravesical nanoparticle albumin-bound paclitaxel in the treatment of bacillus Calmette-Guérin refractory nonmuscle invasive bladder cancer. J Urol; 2011; 186,
26. Bruce, JY; Eickhoff, J; Pili, R et al. A phase II study of 2-methoxyestradiol nanocrystal colloidal dispersion alone and in combination with sunitinib malate in patients with metastatic renal cell carcinoma progressing on sunitinib malate. Invest New Drugs; 2012; 30,
27. Harrison, MR; Hahn, NM; Pili, R et al. A phase II study of 2-methoxyestradiol (2ME2) NanoCrystal® dispersion (NCD) in patients with taxane-refractory, metastatic castrate-resistant prostate cancer (CRPC). Invest New Drugs; 2011; 29,
28. Pfrieger, FW. TeamTree analysis: a new approach to evaluate scientific production. PLoS ONE; 2021; 16,
29. Wang AJY, Yan C, Reike MJ, Black PC, Contreras-Sanz A. A systematic review of nanocarriers for treatment of urologic cancers. Urol Oncol. Published online December 30, 2023.
30. Gheibihayat, SM; Jaafari, MR; Hatamipour, M; Sahebkar, A. Improvement of the pharmacokinetic characteristics of liposomal doxorubicin using CD47 biomimickry. J Pharm Pharmacol; 2021; 73,
31. Sarkar, M; Wang, Y; Ekpenyong, O; Liang, D; Xie, H. Pharmacokinetic behaviors of soft nanoparticulate formulations of chemotherapeutics. Wiley Interdiscip Rev Nanomed Nanobiotechnol; 2023; 15,
32. McMenemin, R; Macdonald, G; Moffat, L; Bissett, D. A phase II study of caelyx (liposomal doxorubicin) in metastatic carcinoma of the prostate: tolerability and efficacy modification by liposomal encapsulation. Invest New Drugs; 2002; 20,
33. Harris, KA; Harney, E; Small, EJ. Liposomal doxorubicin for the treatment of hormone-refractory prostate cancer. Clin Prostate Cancer; 2002; 1,
34. Fosså, SD; Vaage, S; Letocha, H et al. Liposomal doxorubicin (Caelyx) in symptomatic androgen-independent prostate cancer (AIPC)–delayed response and flare phenomenon should be considered. Scand J Urol Nephrol; 2002; 36,
35. Winquist, E; Ernst, DS; Jonker, D et al. Phase II trial of pegylated-liposomal doxorubicin in the treatment of locally advanced unresectable or metastatic transitional cell carcinoma of the urothelial tract. Eur J Cancer; 2003; 39,
36. Sridhar, SS; Blais, N; Tran, B et al. Efficacy and safety of nab-paclitaxel vs paclitaxel on survival in patients with platinum-refractory metastatic urothelial cancer: The Canadian Cancer Trials Group BL.12 Randomized Clinical Trial. JAMA Oncol; 2020; 6,
37. Voss, MH; Hussain, A; Vogelzang, N et al. A randomized phase II trial of CRLX101 in combination with bevacizumab versus standard of care in patients with advanced renal cell carcinoma. Ann Oncol; 2017; 28,
38. Kim, H; Niu, L; Larson, P et al. Polymeric nanoparticles encapsulating novel TLR7/8 agonists as immunostimulatory adjuvants for enhanced cancer immunotherapy. Biomaterials; 2018; 164, pp. 38-53.[COI: 1:CAS:528:DC%2BC1cXjt12qtL8%3D] [DOI: https://dx.doi.org/10.1016/j.biomaterials.2018.02.034] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/29482062]
39. Chai, D; Shan, H; Wang, G et al. Combining DNA vaccine and AIM2 in H1 nanoparticles exert anti-renal carcinoma effects via enhancing tumor-specific multifunctional CD8+ T-cell responses. Mol Cancer Ther; 2019; 18,
40. Zhu, Z; Ma, AH; Zhang, H et al. Phototherapy with cancer-specific nanoporphyrin potentiates immunotherapy in bladder cancer. Clin Cancer Res; 2022; 28,
41. Guo, Q; Dong, Y; Zhang, Y et al. Sequential release of pooled siRNAs and paclitaxel by aptamer-functionalized shell-core nanoparticles to overcome paclitaxel resistance of prostate cancer. ACS Appl Mater Interfaces; 2021; 13,
42. Agathokleous, E; Calabrese, EJ. Evolution of hormesis research: a bibliometric analysis. Arch Toxicol; 2024; 98,
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Abstract
Increasing research efforts are focused on studying the synthesis and mechanisms of nanomedicine in urologic cancer. We performed a bibliometric study of the literature on nanomedicine in urologic cancer over the last 23 years, focusing on aspects such as researchers, institutions, nations, and keywords. We searched for papers in the Web of Science Core Collection from January 1, 2001, to December 29, 2023. Only reviews and original articles written in English were considered. A total of 2386 papers satisfied the given criteria for inclusion. The publications included in the study originated from 90 nations. The United States had the largest number of published papers, accounting for more than 31.01% of the total. The leading institution in this field is the Chinese Academy of Sciences, with a publishing output of 2.35%. Farokhzad, Omid C., is the most prolific author, with 21 articles, and has garnered the most citations, totaling 6271. The latest phrase to enter the top ten most common lists was "gold nanoparticles." We searched for papers in the Web of Science Core Collection from January 1, 2000, to November 28, 2023. Only reviews and original articles written in English were considered. This is the first bibliometric study of nanomedicine in urologic cancer. This article provides a comprehensive analysis of the current state of research on nanomedicine in urologic cancer over the last 23 years. On the basis of this study, future researchers can identify noteworthy publications, journals, and potential collaborators and explore cutting-edge research directions.
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Neither ProQuest nor its licensors make any representations or warranties with respect to the translations. The translations are automatically generated "AS IS" and "AS AVAILABLE" and are not retained in our systems. PROQUEST AND ITS LICENSORS SPECIFICALLY DISCLAIM ANY AND ALL EXPRESS OR IMPLIED WARRANTIES, INCLUDING WITHOUT LIMITATION, ANY WARRANTIES FOR AVAILABILITY, ACCURACY, TIMELINESS, COMPLETENESS, NON-INFRINGMENT, MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE. Your use of the translations is subject to all use restrictions contained in your Electronic Products License Agreement and by using the translation functionality you agree to forgo any and all claims against ProQuest or its licensors for your use of the translation functionality and any output derived there from. Hide full disclaimer
Details
1 Tianjin Medical University General Hospital, Department of Urology, Tianjin, China (GRID:grid.412645.0) (ISNI:0000 0004 1757 9434)
2 Qingdao Central Hospital, University of Health and Rehabilitation Sciences, Department of Urology, Qingdao, People’s Republic of China (GRID:grid.415468.a) (ISNI:0000 0004 1761 4893)