Page - (000388) - in Biomedical Chemistry: Current Trends and Developments

Since DCs have the intrinsic ability of phagocyting foreign material, passive DC targeting for cancer immunotherapy is possible by directing the nanoparticles to sites rich in DCs. For this purpose, the route of administration of the nanoparticles is very important. For example, while subcutaneously administered small nanoparticles (< 100 nm) can be quickly transported into the lymphatic system to interact with the DC localized in the lymph node (Cubas, 2009; Manolova, 2008; Reddy, 2007), larger nanoparticles (> 500 nm) stay for a longer time in the injection site of the skin and predominantly interact with the DCs or monocytes available in the skin (Manolova, 2008; Moon, 2012). To avoid the size dependency of passive DC targeting to the lymph node, direct injection into the blood is suggested as an efficient way to reach both blood and splenic DCs and induce strong immune responses by a variety of particles (Perche, 2011; Tacken, 2011). However, the macrophage uptake is still one of the main drawbacks of the cancer immunotherapy using this strategy. DCs also express many cell surface receptors, such as mannose (Chenevier, 2002; Ramakrishna, 2004), CD11c (Cruz, 2014), DEC-205 (Cruz, 2014), Langerin (Flacher, 2010), DC-SIGN (Cruz, 2010; Varga, 2013), clec9A (Caminschi, 2008), and DCIR2 (Dudziak, 2007), which can facilitate actively targeted cellular endocytosis of the nanoparticles via appropriate surface modification with the ligands that target these receptors on the surface of the DCs (Foged, 2002). It has already been reported that the conjugation of such targeting moieties on the surface of the nanoparticles increases their uptake by the DCs and enhances the DC maturation, as evidenced by the high secretion of cytokine and up- regulation of CD83 and CD86 surface maturation markers (Kempf, 2003). The type of the target receptor can have a substantial effect on the immunological response of nano-immunotherapeutics. A study by Dudziak showed that the targeting antigens to DEC-205 results mainly in cross-presentation of antigens to the CD8 T cells, whereas antigens targeted to DCIR2 are preferentially presented via the MHC class II molecules to the CD4 T cells (Dudziak, 2007). In addition, Idoyaga (Idoyaga, 2011) have shown that, while antigens can be targeted to the splenic CD8α+ DC subset by antigen conjugation to antibodies against Langerin and DEC205, DCIR2 antibodies can specifically target CD8α‒