Seite - (000376) - in Biomedical Chemistry: Current Trends and Developments

in the system, consequently inducing the interaction between the ligand and the antigen (Callard, 1977; Liu, 2007), and also stimulates the overexpression of the receptor at the cells’ surface, therefore resulting in an enhanced internalization of the actively targeted nanoparticles by the tumor cells. Nevertheless, various aspects, including the inappropriate orientation of the targeting ligand, the steric hindrance of subjacent molecules and a competitive behavior towards the receptor binding may revert this relation between the ligand density and the efficiency of cell association (James, 1981; Valdez, 2000). 3.5.3.2.3 Ligands for Tumor Active Targeting The adequate selection of the most suitable targeting moiety to functionalize the surface of nanoparticles is absolutely imperative for the efficiency of their targeting to specific receptors overexpressed by the tumor tissues, therefore representing one of the major aspects to be considered during the design of actively-targeted nanomedicines. A variety of targeting moieties are available to functionalize the surface of carriers through different approaches, and those encompass monoclonal antibodies and their fragments, proteins and peptides, aptamers and other nucleic acids, as well as small molecules (Yu, 2010). 3.5.3.2.3.1 Monoclonal Antibodies In the past few years, monoclonal antibodies (mAb) have remained the preferred and most extensively used and investigated type of targeting moieties, due to the high affinity and specificity they render to the nanoparticles. This potential of the application of mAb in targeted cancer therapy led to the approval of a large number of these macromolecules for clinical use, including rituximab, cetuximab and trastuzumab, as well as to the recent development of chimeric and humanized derivatives with modulated immunogenicity (Kamaly, 2012; Ndungu, 2012; Yoshida, 2010). However, despite the aforementioned attractive features of mAb for targeting anti-tumor nanotherapy, the performance of these molecules in vivo still present some limitations and challenges, including their large size and molecular weight, their immunogenicity resulting in the prompt recognition by the RES and