title: Lipid-enveloped zinc phosphate hybrid nanoparticles for codelivery of H-2K(b) and H-2D(b)-restricted antigenic peptides and monophosphoryl lipid A to induce antitumor immunity against melanoma.
abstract: Nanoimmunotherapy, the application of nanotechnology for sustained and targeted delivery of antigens to dendritic cells (DCs), has attracted much attention in stimulating antigen-specific immune response for antitumor therapy. In order to in situ deliver antigens to DCs for efficient antigen presentation and subsequent induction of strong cytotoxic T lymphocytes (CTL) response, here we developed a multi-peptide (TRP2180-188 and HGP10025-33) and toll-like receptor 4 agonist (monophosphoryl lipid A) codelivery system based on lipid-coated zinc phosphate hybrid nanoparticles (LZnP NPs). This delivery system equips with the chelating property of zinc to realize the high encapsulation efficiency with antigenic peptides and the influence on immune system with adjuvant-like feature. The combination of H-2K(b) and H-2D(b)-restricted peptides could provide multiple epitopes as the target of specific MHC alleles, making tumor more difficult to escape from the surveillance of immune system. The formulated LZnP nano-vaccine with the size of 30nm and outer leaflet lipid exhibited antitumor immunity as the secretion of cytokines in vitro and increased CD8(+) T cell response from IFN-γ ELISPOT analysis ex vivo. The antitumor effects were further evidenced from the prophylactic, therapeutic and metastatic melanoma tumor models compared with free antigens and single peptide-loaded nano-vaccines. These results validate the benefit of LZnP-based vaccine for antitumor immunity and indicate that co-delivery of tumor antigens along with adjuvant may be an optimized strategy for tumor immunotherapy.
authors.affiliation: Tongji School of Pharmacy, PR China.
authors.forename: Xiangting
authors.initials: X
authors.lastname: Zhuang
authors.affiliation: Tongji School of Pharmacy, PR China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Wu
authors.affiliation: Tongji School of Pharmacy, PR China.
authors.forename: Yongdan
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Tongji School of Pharmacy, PR China.
authors.forename: Xiaomeng
authors.initials: X
authors.lastname: Hu
authors.affiliation: Tongji School of Pharmacy, PR China.
authors.forename: Yuling
authors.initials: Y
authors.lastname: Bao
authors.affiliation: Tongji School of Pharmacy, PR China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Tongji School of Pharmacy, PR China.
authors.forename: Qingle
authors.initials: Q
authors.lastname: Song
authors.affiliation: Tongji School of Pharmacy, PR China; National Engineering Research Center for Nanomedicine, PR China; Hubei Engineering Research Center for Novel Drug Delivery System, HuaZhong University of Science and Technology, Wuhan 430030, PR China.
authors.forename: Gao
authors.initials: G
authors.lastname: Li
authors.affiliation: Tongji School of Pharmacy, PR China.
authors.forename: Songwei
authors.initials: S
authors.lastname: Tan
authors.affiliation: Tongji School of Pharmacy, PR China; National Engineering Research Center for Nanomedicine, PR China; Hubei Engineering Research Center for Novel Drug Delivery System, HuaZhong University of Science and Technology, Wuhan 430030, PR China. Electronic address: zhipingzhang@hust.edu.cn.
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000627:therapeutic use; D000818:Animals; D000951:Antigens, Neoplasm / Q000008:administration & dosage / Q000627:therapeutic use; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000627:therapeutic use*; D016207:Cytokines / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology / Q000473:pathology; D004337:Drug Carriers / Q000737:chemistry*; D005260:Female; D006801:Humans; D007167:Immunotherapy; D008050:Lipid A / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008545:Melanoma / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000737:chemistry; D010455:Peptides / Q000008:administration & dosage / Q000627:therapeutic use*; D010710:Phosphates / Q000737:chemistry*; D051197:Toll-Like Receptor 4 / Q000819:agonists; D017967:Zinc Compounds / Q000737:chemistry*
chemical_list: D000276:Adjuvants, Immunologic; D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D016207:Cytokines; D004337:Drug Carriers; D008050:Lipid A; D010455:Peptides; D010710:Phosphates; D051197:Toll-Like Receptor 4; D017967:Zinc Compounds; C043952:zinc phosphate; C048436:monophosphoryl lipid A
keywords: Adjuvant; Cancer immunotherapy; Dendritic cell; Nanoparticles; Tumor antigen