Exploiting immunostimulatory mechanisms of immunogenic cell death to develop membrane-encapsulated nanoparticles as a potent tumor vaccine
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Published:2023-09-08
Issue:1
Volume:21
Page:
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ISSN:1477-3155
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Container-title:Journal of Nanobiotechnology
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language:en
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Short-container-title:J Nanobiotechnol
Author:
Liu Qingwen,Hu Yongmao,Zheng Peng,Yang Ying,Fu Yuting,Yang Ying,Duan Biao,Wang Mengzhen,Li Duo,Li Weiran,He Jinrong,Zheng Xiao,Long Qiong,Ma Yanbing
Abstract
AbstractVaccine is one of the most promising strategies for cancer immunotherapy; however, there are no therapeutic cancer vaccine achieving significant clinical efficacy till now. The main limiting factors include the immune suppression and escape mechanisms developed by tumor and not enough capacity of vaccines to induce a vigorous anti-tumor immunity. This study aimed to develop a strategy of membrane-based biomimetic nanovaccine and investigate the immunological outcomes of utilizing the unique immunostimulatory mechanisms derived of immunogenic cell death (ICD) and of fulfilling a simultaneous nanoscale delivery of a highlighted tumor antigen and broad membrane-associated tumor antigens in the vaccine design. TC-1 tumor cells were treated in vitro with a mixture of mitoxantrone and curcumin for ICD induction, and then chitosan (CS)-coated polylactic co-glycolic acid (PLGA) nanoparticles loaded with HPV16 E744-62 peptides were decorated with the prepared ICD tumor cell membrane (IM); further, the IM-decorated nanoparticles along with adenosine triphosphate (ATP) were embedded with sodium alginate (ALG) hydrogel, And then, the immunological features and therapeutic potency were evaluated in vitro and in vivo. The nanovaccine significantly stimulated the migration, antigen uptake, and maturation of DCs in vitro, improved antigen lysosome escape, and promoted the retention at injection site and accumulation in LNs of the tumor antigen in vivo. In a subcutaneously grafted TC-1 tumor model, the therapeutic immunization of nanovaccine elicited a dramatical antitumor immunity. This study provides a strategy for the development of tumor vaccines.
Graphical Abstract
Funder
the Science and Technology Project of Yunnan Province
the National Natural Science Foundation of China
the CAMS Initiative for Innovative Medicine
the Yunnan Province Major Science and Technology Special Project
the Yunnan High-level Health and Technical Personnel Project
Publisher
Springer Science and Business Media LLC
Subject
Pharmaceutical Science,Applied Microbiology and Biotechnology,Biomedical Engineering,Molecular Medicine,Medicine (miscellaneous),Bioengineering
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