Abstract
In recent years, polymeric nanoparticles have appeared as a most viable and versatile delivery system for targeted cancer therapy. Various in vivo studies have demonstrated that virus-sized stealth particles are able to circulate for a prolonged time and preferentially accumulate in the tumor site via the enhanced permeability and retention (EPR) effect (so-called "passive tumor-targeting"). The surface decoration of stealth nanoparticles by a specific tumor-homing ligand, such as antibody, antibody fragment, peptide, aptamer, polysaccharide, saccharide, folic acid, and so on, might further lead to increased retention and accumulation of nanoparticles in the tumor vasculature as well as selective and efficient internalization by target tumor cells (termed as "active tumor-targeting"). Notably, these active targeting nanoparticulate drug formulations have shown improved, though to varying degrees, therapeutic performances in different tumor models as compared to their passive targeting counterparts. In addition to type of ligands, several other factors such as in vivo stability of nanoparticles, particle shape and size, and ligand density also play an important role in targeted cancer chemotherapy. In this review, concept and recent development of polymeric nanoparticles conjugated with specific targeting ligands, ranging from proteins (e.g., antibodies, antibody fragments, growth factors, and transferrin), peptides (e.g., cyclic RGD, octreotide, AP peptide, and tLyp-1 peptide), aptamers (e.g., A10 and AS1411), polysaccharides (e.g., hyaluronic acid), to small biomolecules (e.g., folic acid, galactose, bisphosphonates, and biotin), for active tumor-targeting drug delivery in vitro and in vivo are highlighted and discussed. With promise to maximize therapeutic efficacy while minimizing systemic side effects, ligand-mediated active tumor-targeting treatment modality has become an emerging and indispensable platform for safe and efficient cancer therapy.
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