title: Erythrocyte Membrane-Enveloped Polymeric Nanoparticles as Nanovaccine for Induction of Antitumor Immunity against Melanoma.
abstract: Cancer immunotherapy is mainly focused on manipulating patient's own immune system to recognize and destroy cancer cells. Vaccine formulations based on nanotechnology have been developed to target delivery antigens to antigen presenting cells (APCs), especially dendritic cells (DCs) for efficiently induction of antigen-specific T cells response. To enhance DC targeting and antigen presenting efficiency, we developed erythrocyte membrane-enveloped poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles for antigenic peptide (hgp10025-33) and toll-like receptor 4 agonist, monophosphoryl lipid (MPLA). A Mannose-inserted membrane structure was constructed to actively target APCs in the lymphatic organ, and redox-sensitive peptide-conjugated PLGA nanoparticles were fabricated which prone to cleave in the intracellular milieu. The nanovaccine demonstrated the retained protein content in erythrocyte and enhanced in vitro cell uptake. An antigen-depot effect was observed in the administration site with promoted retention in draining lymph nodes. Compared with other formulations after intradermal injection, the nanovaccine prolonged tumor-occurring time, inhibited tumor growth, and suppressed tumor metastasis in prophylactic, therapeutic, and metastatic melanoma models, respectively. Additionally, we revealed that nanovaccine effectively enhanced IFN-γ secretion and CD8(+) T cell response. Taken together, these results demonstrated the great potential in applying an erythrocyte membrane-enveloped polymeric nanoplatform for an antigen delivery system in cancer immunotherapy.
authors.affiliation: †Tongji School of Pharmacy, §Hubei Engineering Research Center for Novel Drug Delivery System, ‡National Engineering Research Center for Nanomedicine, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Guo
authors.affiliation: †Tongji School of Pharmacy, §Hubei Engineering Research Center for Novel Drug Delivery System, ‡National Engineering Research Center for Nanomedicine, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Wang
authors.affiliation: †Tongji School of Pharmacy, §Hubei Engineering Research Center for Novel Drug Delivery System, ‡National Engineering Research Center for Nanomedicine, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Qingle
authors.initials: Q
authors.lastname: Song
authors.affiliation: †Tongji School of Pharmacy, §Hubei Engineering Research Center for Novel Drug Delivery System, ‡National Engineering Research Center for Nanomedicine, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Wu
authors.affiliation: †Tongji School of Pharmacy, §Hubei Engineering Research Center for Novel Drug Delivery System, ‡National Engineering Research Center for Nanomedicine, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Xiangting
authors.initials: X
authors.lastname: Zhuang
authors.affiliation: †Tongji School of Pharmacy, §Hubei Engineering Research Center for Novel Drug Delivery System, ‡National Engineering Research Center for Nanomedicine, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Yuling
authors.initials: Y
authors.lastname: Bao
authors.affiliation: †Tongji School of Pharmacy, §Hubei Engineering Research Center for Novel Drug Delivery System, ‡National Engineering Research Center for Nanomedicine, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Miao
authors.initials: M
authors.lastname: Kong
authors.affiliation: †Tongji School of Pharmacy, §Hubei Engineering Research Center for Novel Drug Delivery System, ‡National Engineering Research Center for Nanomedicine, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Qi
authors.affiliation: †Tongji School of Pharmacy, §Hubei Engineering Research Center for Novel Drug Delivery System, ‡National Engineering Research Center for Nanomedicine, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Songwei
authors.initials: S
authors.lastname: Tan
authors.affiliation: †Tongji School of Pharmacy, §Hubei Engineering Research Center for Novel Drug Delivery System, ‡National Engineering Research Center for Nanomedicine, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000276:immunology; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000737:chemistry*; D003713:Dendritic Cells / Q000276:immunology; D004912:Erythrocytes / Q000737:chemistry; D007167:Immunotherapy / Q000379:methods*; D019344:Lactic Acid / Q000737:chemistry; D008545:Melanoma / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000737:chemistry*; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer
chemical_list: D019496:Cancer Vaccines; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid
keywords: cancer vaccine· red blood cell; dendritic cells·immunotherapy; nanoparticles