Microparticle surface modifications targeting dendritic cells for non-activating applications.
Microparticulate systems for delivery of therapeutics to DCs for immunotherapy have gained attention recently. However, reports addressing the optimization of DC-targeting microparticle delivery systems are limited, particularly for cases where the goal is to deliver payload to DCs in a non-activating fashion. Here, we investigate targeting DCs using poly (d lactide-co-glycolide) microparticles (MPs) in a non-stimulatory manner and assess efficacy in vitro and in vivo. We modified MPs by surface immobilizing DC receptor targeting molecules - antibodies (anti-CD11c, anti-DEC-205) or peptides (P-D2, RGD), where anti-CD11c antibody, P-D2 and RGD peptides target integrins and anti-DEC-205 antibody targets the c-type lectin receptor DEC-205. Our results demonstrate the modified MPs are neither toxic nor activating, and DC uptake of MPs in vitro is improved by the anti-DEC-205 antibody, the anti-CD11c antibody and the P-D2 peptide modifications. The P-D2 peptide MP modification significantly improved DC antigen presentation in vitro both at immediate and delayed time points. Notably, MP functionalization with P-D2 peptide and anti-CD11c antibody increased the rate and extent of MP translocation in vivo by DCs and MΦs, with the P-D2 peptide modified MPs demonstrating the highest translocation. This work informs the design of non-activating polymeric microparticulate applications such as vaccines for autoimmune diseases.
J Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, Gainesville, FL 32611-6131, USA.
Jamal S
JS
Lewis
Toral D
TD
Zaveri
Charles P
CP
Crooks
Benjamin G
BG
Keselowsky
D000818:Animals; D039521:CD11c Antigen / Q000737:chemistry; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology*; D005260:Female; D007167:Immunotherapy / Q000379:methods; D019344:Lactic Acid / Q000737:chemistry; D008024:Ligands; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D008863:Microspheres; D010455:Peptides / Q000737:chemistry; D010587:Phagocytosis; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011485:Protein Binding; D013499:Surface Properties; D014612:Vaccines / Q000737:chemistry
D039521:CD11c Antigen; D016207:Cytokines; D008024:Ligands; D010455:Peptides; D014612:Vaccines; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid