Page - (000374) - in Biomedical Chemistry: Current Trends and Developments

of utmost importance for the efficient targeting and recognition of the targeted receptor, both in vitro and in vivo. This optimal engineering of the nanoparticles’ architecture should encompass not only the physicochemical properties of the nanoplatform, including its size, shape and surface properties (i.e., charge and hydrophobicity), but also parameters associated with the targeting ligand, such as the affinity of the ligand to the targeting receptor, the ligand density and the conjugation chemistry (Berretta, 2011; Chen, 2012; Humrich, 2010; Lesterhuis, 2004; Signori, 2010). The combination of these factors can synergistically impact the systemic circulation kinetics, biodistribution profiles and targeting efficiency of actively-targeted nanodelivery systems, therefore dictating their performance in vivo (Fig. 3.5.10). Figure 3.5.10: The physicochemical properties of the ligand and the nanoparticles affect their blood circulation profiles, their biodistribution and their ability to be internalized by cancer cells. Reproduced with permission from (Bertrand, 2014). The optimization of the targeted nanoparticles’ size is therefore crucial for their extravasation from the tumor vasculature and accumulation at the tumor size. Rationally, when a ligand functionalization is intended, the increase on the hydrodynamic radius after conjugation of the targeting moiety must be taken into consideration, particularly in the case of large ligands, such as antibodies, proteins or aptamers, under penalty of negatively influencing the targeting efficiency by hindering the accumulation of the nanocarrier in the tumor (Humrich, 2010). The