Seite - (000377) - in Biomedical Chemistry: Current Trends and Developments

rapid nanoparticle clearance from the systemic circulation (Taniguchi, 2012; Vivek, 2014), as well as their liability to environmental alterations and organic solvents, which challenges the processes of scale-up and manufacturing, impacts the cost/effectiveness of the formulations and compromises their stability. In this regard, there is an emerging interest on engineering antibody fragments, including Fab fragments, single chain variable fragments (scFv) minibodies, diabodies and nanobodies, for functionalizing the surface of nanodelivery systems, maintaining their targeting specificity and considerably reducing their size and immunogenicity (Peer, 2007; Scott, 2012; Weiner, 2000). Antibody fragment-targeted nanomedicines have already reached clinical trials, as for example MCC-465 and SGT-53 (Table 3.5.3). MCC-465 exhibited an adequate biodistribution and highly efficient delivery of doxorubicin for the treatment of stomach cancer in preclinical studies (Baxevanis, 2008), and SGT-53 sustained the tumor growth in different cancers, including head and neck, breast and prostate, by delivering the p53 supressor protein after targeting the transferrin-receptor (Tf-R) overexpressed by the tumor cells (Bonsignori, 2012; Le Garff-Tavernier, 2014). 3.5.3.2.3.2 Proteins and Peptides Recent advances in bioinformatics and cancer proteomics enabled the high-throughput screening of protein antigens overexpressed in tumors. These biomarkers can be selectively recognized by targeting proteins and peptides that functionalize the nanoparticles’ surface, resulting in their receptor-mediated endocytosis (Mody, 2011). Transferrin (Tf), a serum glycoprotein involved in the iron homeostasis and regulation of cell growth has focused attention for specifically binding to the internalizing transferrin-receptor (Tf-R), approximately 100-fold overexpressed in various tumors comparatively to healthy cells (Chandrasekhar, 2013). Therefore, transferrin has been exploited as a potential ligand for decorating nanoparticulate drug delivery systems intended to target Tf-R and some nano-formulations are presently under clinical evaluation (Prang, 2005). However, the feasibility of using proteins for targeting purposes has been limited by the immunogenicity of these molecules, resulting in their increased predisposition for