title: Surface modification of poly(D,L-lactic-co-glycolic acid) nanoparticles with protamine enhanced cross-presentation of encapsulated ovalbumin by bone marrow-derived dendritic cells.
abstract: Cross-presentation is the key process in stimulation of cytotoxic T lymphocyte (CTL) immune response in eliminating many infectious diseases and tumors. Previous studies have shown that surface modification of poly(D,L-lactic-co-glycolic acid) (PLGA) particles with polycations enhanced their adjuvant ability resulting in a strong antibody response to the encapsulated antigen. However, the in vitro cross-presentation by protamine-coated PLGA nanoparticles (NPs) has not been addressed yet. In this study, a model antigen ovalbumin (OVA) was encapsulated into PLGA nanoparticles, with (OVA-NPs/protamine) or without protamine coating (OVA-NPs). These nanoparticles were then used to stimulate murine bone marrow-derived dendritic cells (BMDCs). Flow cytometry analysis revealed an increase in endocytosis of protamine-coated PLGA nanoparticles by BMDCs at 37°C. Compared with OVA-NPs-treated BMDCs, stimulation with OVA-NPs/protamine led to significantly upregulation of CD80, CD86, and CD83, increased secretion of IL-12p70, and decreased production of IL-4 by BMDCs. Furthermore, OVA-NPs/protamine-treated BMDCs also showed an enhanced cross-presentation to B3Z T cell hybridoma in vitro. Transmission electron microscopy (TEM) study showed that protamine-coated PLGA nanoparticles escaped from lysosomes through the interaction with lysosomal membrane. These results demonstrated that protamine-coated PLGA nanoparticles could enhance the cross-presentation of encapsulated exogenous antigen by facilitating antigen uptake and lysosomal escape, suggesting the feasibility to be a potent adjuvant for cellular vaccines.
authors.affiliation: College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China.
authors.forename: Ruiling
authors.initials: R
authors.lastname: Han
authors.forename: Junming
authors.initials: J
authors.lastname: Zhu
authors.forename: Xiangliang
authors.initials: X
authors.lastname: Yang
authors.forename: Huibi
authors.initials: H
authors.lastname: Xu
mesh_terms: D000818:Animals; D000941:Antigens / Q000276:immunology; D001672:Biocompatible Materials / Q000737:chemistry; D001854:Bone Marrow Cells / Q000276:immunology; D045142:Cross-Priming / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology* / Q000648:ultrastructure; D004339:Drug Compounding; D019344:Lactic Acid / Q000737:chemistry*; D008297:Male; D008422:Materials Testing; D051379:Mice; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000737:chemistry*; D010047:Ovalbumin / Q000276:immunology*; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011479:Protamines / Q000737:chemistry*; D013499:Surface Properties
chemical_list: D000941:Antigens; D001672:Biocompatible Materials; D011479:Protamines; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D010047:Ovalbumin