Page - (000368) - in Biomedical Chemistry: Current Trends and Developments

to tumors. 3.5.3.1.2 Physicochemical Properties of Nanoparticles Affecting the Passive Targeting The physicochemical properties of the nanocarriers, namely the size, surface charge, shape and hydrophobicity, play a major role on exploiting the EPR effect and, consequently, the passive mechanism as a strategy to target tumors, not only for influencing the extravasation capacity of the nanoparticles from the tumor surrounding capillaries and their accumulation in the tumor site, but also, and equally relevant, for influencing their stability in blood circulation, which significantly impacts the clearance by the reticuloendothelial system (RES), and ultimately the blood circulation kinetic profiles (Alexis, 2008; Bertrand, 2012; Dreher, 2006; Maeda, 2001). The meticulous and rational design of the nanoparticles intended for cancer therapeutic and diagnostic applications is, therefore, of utmost importance when taking a passive targeting strategy into consideration. The size of the nanocarriers represents a crucial parameter that significantly influences the extent and kinetics of accumulation in the tumor tissues. In order for the nanoplatforms to extravasate from the tumor microvasculature to the tumor interstitial fluid, their hydrodynamic radius needs to be lower than the threshold of the capillary interendothelial gaps. In contrary, nanoparticles sized over the referred limit are more likely to be engulfed by the RES (Arias, 2011). Recent works have been shown the impact of the nanocarriers size on the efficiency of tumor passive targeting (Cabral, 2011; Huo, 2013; Lee, 2013b; Perrault, 2009; Wong, 2011). Chan evaluated the influence of the nanoparticles’ size and surface chemistry on the in vivo passive targeting of tumors, and it was observed that nanoparticles of reduced size are capable of extravasate to the tumor interstitium, contrarily to their larger counterpartes, which were confined inside the neovasculature (Perrault, 2009). The histological data (Fig.3.5.8) revealed that, although no difference was observed on the extension of tumor penetration by nanoparticles with variable sizes (20, 60 and 100 nm) after 1 h, the smaller particles diffused inside the tumor mass throughout time, while