The major problem associated with chemotherapeutic agents is their lack of specificity and selectivity. This is mainly due to the presence of very subtle metabolic differences between the tumor cells and the normal cells[51]. Hence, very large doses of chemotherapeutic drugs are required for successful chemotherapy. Furthermore, cancer chemotherapy leads to severe adverse effects, such as hair loss, damages to the liver, kidney, and bone marrow, as the normal cells are also exposed to these cytotoxic agents[52]. A lot of research efforts have therefore been directed to improve the specificity of anticancer agents[53, 54]. One of the widely used approach is to selectively administer the drugs to the tissue/organ involved, as in case of intra-arterial
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Passive targeting is one such strategy which exploits the leaky tumor vasculature present in the vicinity of cancer cells[54]. Quick formation of new blood vessels in rapidly growing cancer cells is a common phenomenon. This vasculature formation is inherently defective in nature, which in turn, allows large molecules and lipids to easily enter the extravascular space in tumors[58]. In addition, due to fast development of cancerous cells, lymphatic drainage is undeveloped, leading to retention of large molecules and lipids in the extravascular space of the tumors[58]. This phenomenon is termed as enhanced permeability and retention (EPR) effect[59]. Another approach that is widely used to deliver drugs is the active targeting approach which is based on the targeting of drugs to the overexpressed receptors on cancer cells [60] [61, 62]. Tumor cells require various nutrients and vitamins for rapid development, and hence they overexpress many tumor-specific receptors, which can be used as targets to deliver cytotoxic agents into tumors[63]. Various ligands or active targeting agents used are antibodies, growth factors (vascular endothelial growth factor), receptors (such as transferrin, epidermal growth factor receptor), ligands (including peptides and small synthetic organic molecules), nutrient
Passive targeting is one such strategy which exploits the leaky tumor vasculature present in the vicinity of cancer cells[54]. Quick formation of new blood vessels in rapidly growing cancer cells is a common phenomenon. This vasculature formation is inherently defective in nature, which in turn, allows large molecules and lipids to easily enter the extravascular space in tumors[58]. In addition, due to fast development of cancerous cells, lymphatic drainage is undeveloped, leading to retention of large molecules and lipids in the extravascular space of the tumors[58]. This phenomenon is termed as enhanced permeability and retention (EPR) effect[59]. Another approach that is widely used to deliver drugs is the active targeting approach which is based on the targeting of drugs to the overexpressed receptors on cancer cells [60] [61, 62]. Tumor cells require various nutrients and vitamins for rapid development, and hence they overexpress many tumor-specific receptors, which can be used as targets to deliver cytotoxic agents into tumors[63]. Various ligands or active targeting agents used are antibodies, growth factors (vascular endothelial growth factor), receptors (such as transferrin, epidermal growth factor receptor), ligands (including peptides and small synthetic organic molecules), nutrient