Page - (000373) - in Biomedical Chemistry: Current Trends and Developments

diaminocyclohexane-platinum. 3.5.3.2 Active Targeting 3.5.3.2.1 The Fundamentals of Active Targeting The active targeting of nanoparticles, also denominated ligand- mediated targeting, involves the surface-functionalization of the nanoparticles with active moieties possessing intrinsic affinity to specific receptors/antigens overexpressed in the diseased tissues or cells, functioning not only as driven-force for the nanocarries’ accumulation at the target site, but also as a mechanism for enhanced cellular association and internalization by receptor-mediated endocytosis (Fig. 3.5.7B) (ACS, 2014; Allen, 2002; Arias, 2011; Cho, 2008; Couvreur, 2006; Danhier, 2010; Kamaly, 2012; Lammers, 2012; Peer, 2007; Shi, 2011; Torchilin, 2006). Considering the specific cellular recognition and consequent enhancement of cellular uptake as the main achievement of the active targeting, this strategy is assumed to ultimately result in an improved therapeutic efficacy of the targeted nanoparticulate systems, comparatively to their non-targeted counterparts (Kamaly, 2012). The active targeting mechanism requires the proximity of the ligand-anchored nanoparticles to the targeted antigen, enabling their recognition and the interaction between the two components. Therefore, the intrinsic characteristics of the nanocarriers influencing the EPR effect and the blood circulation kinetics also play an important role on the delivery and therapeutic and efficiency of active- targeted nanoparticles, since those primarily need to extravasate from the tumor microvasculature in order to interact with their specific targets located in the extravascular tissue (Lammers, 2012; Taurin, 2012). Hence, the active and passive strategies for targeting of nanoparticles to tumors are currently considered as complementary to ultimately improve the therapeutic efficiency of anticancer nanodelivery systems. 3.5.3.2.2 Factors Affecting Tumor Active Targeting The meticulous and rational design of actively targeted nanocarriers is