title: Bioreducible alginate-poly(ethylenimine) nanogels as an antigen-delivery system robustly enhance vaccine-elicited humoral and cellular immune responses.
abstract: Although polysaccharide nanogels have emerged as a novel antigen delivery system for vaccine development, whether modulating the redox sensitivity of nanogels could improve vaccine efficacy remains unclear. In the present study, we generated bioreducible cationic alginate-polyethylenimine (PEI) nanogels as a novel vaccine delivery system. Briefly, nanogels were prepared by the electrostatic interaction of negatively charged alginate sodium with branched PEI2k, followed by disulfide cross-linking to generate bioreducible nanogels (AP-SS). The AP-SS nanogels demonstrated great antigen-loading capacity and minimal cytotoxicity. The in vitro study showed that reducible AP-SS nanogels not only facilitated antigen uptake by mouse bone marrow dendritic cells (BMDCs), but also promoted intracellular antigen degradation and cytosolic release. Moreover, AP-SS nanogels significantly enhanced both MHC class I and II antigen presentation by BMDCs. Compared with the non-reducible nanogels, AP-SS nanogels more potently enhanced vaccine-induced antibody production and CD8+ T cell-mediated tumor cell lysis. Hence, the bioreducible alginate-PEI nanogels could serve as a potent adjuvant to improve vaccine-elicited humoral and cellular immune responses.
authors.affiliation: Key Laboratory of Cancer Nanotechnology, Shenzhen Innovative Pharmacology and Biotherapy Pre-clinical Test Public Service Platform, Shenzhen Institutes of Advance Technology, Chinese Academy of Science, PR China.
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.forename: Zichao
authors.initials: Z
authors.lastname: Luo
authors.forename: Peng
authors.initials: P
authors.lastname: Liu
authors.forename: Ningning
authors.initials: N
authors.lastname: Gao
authors.forename: Yijuan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Hong
authors.initials: H
authors.lastname: Pan
authors.forename: Lanlan
authors.initials: L
authors.lastname: Liu
authors.forename: Ce
authors.initials: C
authors.lastname: Wang
authors.forename: Lintao
authors.initials: L
authors.lastname: Cai
authors.forename: Yifan
authors.initials: Y
authors.lastname: Ma
mesh_terms: D000464:Alginates / Q000008:administration & dosage* / Q000737:chemistry; D000818:Animals; D017951:Antigen Presentation; D000941:Antigens / Q000008:administration & dosage*; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology; D016503:Drug Delivery Systems; D005260:Female; D005782:Gels; D020723:Glucuronic Acid / Q000008:administration & dosage / Q000737:chemistry; D006603:Hexuronic Acids / Q000008:administration & dosage / Q000737:chemistry; D007074:Immunoglobulin G / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology; D015848:Interleukin-5 / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000008:administration & dosage*; D011094:Polyethyleneimine / Q000008:administration & dosage* / Q000737:chemistry; D013154:Spleen / Q000166:cytology; D014612:Vaccines / Q000008:administration & dosage*
chemical_list: D000464:Alginates; D000941:Antigens; D005782:Gels; D006603:Hexuronic Acids; D007074:Immunoglobulin G; D015848:Interleukin-5; D014612:Vaccines; D007371:Interferon-gamma; D020723:Glucuronic Acid; D011094:Polyethyleneimine; D010047:Ovalbumin