Seite - (000375) - in Biomedical Chemistry: Current Trends and Developments

size of targeted nanoparticles was also revealed to impact their intracellular trafficking, with smaller particles being increasingly found deposited in the cytoplasm and nucleus of cancer cells, in a study conducted by Lee (Kapsenberg, 2003). In parallel, the influence of the shape of actively targeted nanoparticles on their cell internalization by cancer cells has also been recently investigated (Coosemans, 2014; Hanke, 2013; Subbotin, 2014). The surface of the actively targeted nanoparticles also impact on the interaction between those and the targeted cells’ surface, therefore contributing for the efficacy of the targeting. Cationic nanoparticulate systems are acknowledged for more extensively interacting with negatively-charged cell membranes, resulting in a non-specific increased cellular association and internalization (Offringa, 2009). However, an excess in the positive charge of the nanoparticles might increase toxicity and stimulate immunologic response (Moghimi, 2005). When the nanoparticles’ surface is functionalized with a targeting moiety, the surface charge is not only influenced by the intrinsic charge of the ligand and the nanoplatform, but also by the ligand density. Besides the surface charge, the hydrophobicity of the nanocarriers can also interfere with the way they interact with targeted cells, since the adsorption of plasma proteins onto the surface of non-sterically stabilized nanoparticles may decrease the capacity of those to bind to the targeted receptor (Homma, 2005). Contrarily, the nanoparticles’ surface functionalization with high molecular weight polymers, such as PEG, may hinder the targeting moieties to efficiently bind to their antigen (Lowin, 1995; Peters, 1991). The development of a PEG-shielded actively-targeted nanoplatform with prolonged circulation time and capable of undergoing cleavage of the steric protection in the tumor interstitium, consequently exposing the targeting moiety to the cancer cells, might constitute an interesting approach demanding further investigation (Arroyo, 2002). Finally, the density of the targeting molecules functionalizing the nanoparticles’ surface significantly influences the avidity of targeting nanotherapeutics to the complementary receptor. Theoretically, a higher density of the targeting moieties generates a favorable binding enthalpy