Seite - (000366) - in Biomedical Chemistry: Current Trends and Developments

both passive and active mechanisms for targeting an extensive variety of malignant tissues (Fig. 3.5.7) (Davis, 2008; Farokhzad, 2009; Ferrari, 2005; Nicolas, 2013). This section briefly describes the fundamentals behind tumor targeting, scrutinizes different strategies that have been employed for targeting cancer tissues, and highlights the most recent breakthroughs on designing and developing targeting drug delivery nanoplatforms for application in cancer therapy. Figure 3.5.7: Strategies adopted for drug targeting and localization of nanosystems to tumor cells and tissues. (A) Passive targeting. Circulating nanoparticles passively extravasate in solid tumor tissue via the enhanced permeability of blood vessels, i.e., through the disorganized and leaky vasculature surrounding the solid tumor coupled with the absence of lymphatic drainage, and preferentially accumulate in tumor cells (the EPR effect). (a) The drug is released into the extracellular matrix and diffuses through the cells and tissue. (B) Active targeting. Once nanoparticles passively extravasate and concentrate in the target tissue via the EPR effect, the presence of ligands grafted onto the nanoparticle surface enable active targeting of xthe nanoparticles to receptors that are overexpressed on tumor cells or tissue, resulting in enhanced uptake and internalization via receptor-mediated endocytosis. (b) Tumor-specific ligands on the nanoparticles bind to cell surface receptors, triggering internalization of the nanoparticles into the cell through endosomes on which, due to an internal acidic pH, the drug is released from the nanoparticles and diffuses into the cytoplasm. (C) Active targeting to endothelial cells. Nanoparticles can be targeted to bind to angiogenic endothelial cell surface receptors with the aims of enhancing drug accumulation in the tumor endothelium, thereby inhibiting growth of blood vessels supplying the tumor rather than inhibiting tumor cells per se (c); and improving delivery of chemotherapeutic agents to tumor cells via the EPR effect with the potential to act synergistically in targeting both the vascular tissue and tumor cells. Adapted