Page - (000379) - in Biomedical Chemistry: Current Trends and Developments

technique has been used by Langer and Farokhzad for developing customized controlled-release nanoplatforms capable of specifically targeting the prostate-specific membrane antigen (PMSA) (Ferris, 2010; Ma, 2013; Monjanel, 2014; Nembrini, 2011; Tao, 2012). Aptamers present attractive intrinsic features to be used as targeting ligands, such as smaller size and reduced immugenicity, in comparison with mAb or other macromolecules, resulting in improved stability and biodistribution profiles (Oki, 2012; Pawelec, 1999). Similarly to the other classes of targeting moieties, the use of aptamers presents some limitations, which hinder their clinical success. First of all, the susceptibility of nucleic acids to the action of nucleases, the stability of the aptamer conjugation onto the nanoparticles’ surface becomes a major concern. Second of all, the negative charge of the aptamers attributed to the phosphodiester backbone is suspected to impact the systemic circulation kinetics of the actively-targeted nanosystem. Finally, although presenting a relatively small molecular size, the stiffness of the nucleic acid conformation may be translated into an increased hydrodynamic radius of the targeting nanosystem after ligand conjugation, hence influencing its accumulation at the targeted site, as previously discussed in this section. 3.5.3.2.3.4 Small Molecules Small molecules, usually defined as possessing a molecular weight < 500 Da, are currently considered as a potential group of targeting moieties, due to the attractiveness of their properties. These targeting molecules present a small size, improved stability, and almost no immunogenicity. In addition, the availability of simple coupling chemistries for their conjugation onto the nanoparticles’ surface enable the control of the functionalization process and, consequently, the fine- tuning of the ligand density and charge on the nanosystems’ surface, which play a significant role in the stability, blood circulation kinetics and targeting efficiency, as previously discussed. Furthermore, a wide range of ligands with different physiochemical properties and chemical functionalities are available and the low production costs, reproducible scale-up and simple manufacturing render these small molecular weight compounds very promising targeting ligands for tumor targeted therapy