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Figure 1. Different types of nanocarrier structures.
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Figure 2. Passive targeting and active targeting for drug delivery to solid tumors.
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Figure 3. Mechanism of the drug release when reaching the tumor site (1-3).
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Figure 4. Types of active ligands used for active targeting. RGD: Arginine-glycine-aspartate.
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Figure 5. Different strategies for surface modifications from the conventional nanoparticles. NP: Nanoparticle; PEG: Poly(ethylene glycol).
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Over the past few decades, interest in designing and developing nanosized drug delivery systems (also known as nanocarriers) has undergone considerable explosion. Indeed, these nanocarriers provide potential solutions to improve cancer chemotherapy by over-riding the poor biopharmaceutical properties of drugs, and by altering the pharmacokinetic and biodistribution of conventional cytotoxic molecules [1]. However, the pharmaceutical application of these systems in systemic administration is usually limited, owing to their rapid elimination from the blood circulation, resulting from a nonspecific uptake by the mononuclear phagocyte system (MPS) [2,3]. Consequently, in order to overcome the opsonization of nanocarriers, a number of widely used and effective methods have been investigated to render nanocarriers 'invisible' to the immune system, creating long-circulating nanoparticles (NPs), known as stealth NPs. Interestingly, by coating the nanoparticulate surface with poly(ethylene glycol) (PEG), referred to as a PEGylation process, NPs exhibited decreased levels of uptake by the MPS and, consequently, an increased circulation time in the blood, allowing passive targeting of the tumors [2,4]. Furthermore, surface modification of NPs with PEG moieties has emerged as a platform for the incorporation of active-targeting ligands, thereby providing the drug carriers with specific tumor-targeting properties [5].
In this article, the interest of stealth NPs will be described. Nanocarriers that will be considered include liposomes (vesicles in which an aqueous volume is entirely surrounded by a bilayer phospholipid membrane), micelles (self-assembly of amphiphiles that form supramolecular core-shell structures in the aqueous environment), polymer NPs (including nanospheres and nanocapsules) and lipid NPs (a biocompatible lipid core that is present under solid matrix [i.e., solid lipid NPs], or a liquid oily core surrounded by surfactant [i.e., lipid nanocapsules]) (Figure 1).
Specifically, this article classifies the various anticancer drug families incorporated into stealth NPs that have...