Page - (000386) - in Biomedical Chemistry: Current Trends and Developments

carboxyphenoxy) hexane (CPH) with inherent adjuvant properties for immunogenicity, antigen-loading properties and antitumor activity. It was shown that mice treated with ovalbumin-encapsulated CPTEG:CPH particles elicited very high CD8+ T cell responses on days 14 and 20, leading to a delay of the tumor progression and extended survival time. These results suggest that the immunoadjuvant properties of the nanoparticles can enhance antigen-specific immuno-cellular responses, and thus, they can be potentially applied for the promotion of antitumor responses in cancer patients. 3.5.4.3 Nanoparticle Based DC Targeting for Cancer Immunotherapy Nanoparticles have attracted more attention than microparticles for DC targeting because of the inverse relationship between the efficiency of the uptake by DCs and the particle size (Hamdy, 2011). Moreover, positively charged nanoparticles are more preferred since they can highly interact with the immune cells via binding to the negatively charged surface of the cells (Dobrovolskaia, 2012; Gjetting, 2014). After the internalization of nanoparticles into the DCs, loaded cancer cell antigens can be released in endosomes, degrade, and eventually bind to the MHC II molecules on the surface of the DCs to present the antigenic molecules to the CD4+ T cells (Trombetta, 2005). If the nanoparticles escape from the endosome and release their immunostimulative antigens in the cytoplasm, antigens degrade to small peptides by the proteosomes and, finally, form a complex with the MHC I in order to be recognized by the CD8+ T cells (Davis, 2004; Trombetta, 2005). Finally, activated T cells can recognize cancer cells expressing antigens on their surface and destroy them. These explanations show the substantial role of the nanoparticle uptake by DCs for the subsequent immune cell activation. For example, Ma (Ma, 2012) have shown that tumor antigenic peptides loaded in PLGA nanoparticles can be highly colocalized in the DCs in 30 min (Fig. 3.5.11) and induce significantly stronger antitumor cytotoxicity of T lymphocytes than the free antigen peptide. DC targeting can be achieved via both passive and active processes. The efficiency of the anticancer nanovaccines to passively target DCs is strongly dependent on the size, surface charge,