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Injectable versatile liquid-solid transformation implants alliance checkpoint blockade for magnetothermal dynamic-immunotherapy

Authors :
Mengna Wang
Siyu Deng
Yijia Cao
Hang Zhou
Wei Wei
Kexiao Yu
Youde Cao
Bing Liang
Source :
Materials Today Bio, Vol 16, Iss , Pp 100442- (2022)
Publication Year :
2022
Publisher :
Elsevier, 2022.

Abstract

The ongoing circulating energy loss, low reactive oxygen species (ROS) accumulation and poor immunogenicity of tumors make it difficult to induce sufficient immunogenic cell death (ICD) in the tumor immunosuppressive microenvironment (TIME), resulting in unsatisfactory immunotherapy efficacy. Furthermore, for highly malignant tumors, simply enhancing ICD is insufficient for exhaustively eliminating the tumor and inhibiting metastasis. Herein, we propose a unique magnetothermal-dynamic immunotherapy strategy based on liquid-solid transformation porous versatile implants (Fe3O4/AIPH@PLGA) that takes advantage of less energy loss and avoids ongoing circulating losses by minimally invasive injection into tumors. In addition, the magnetothermal effect regresses and eliminates tumors that are not limited by penetration to simultaneously trigger 2,2′-azobis[2-(2-imidazolin-2-yl) propane] dihydrochloride (AIPH) decomposition and generate a large amount of oxygen-irrelevant free radicals and heat shock protein (HSP) accumulation by heating, evoking both intracellular oxidative stress and endoplasmic reticulum (ER) stress to induce large-scale ICD and enhance tumor immunogenicity. More importantly, in orthotopic bilateral breast tumor models, a significant therapeutic effect was obtained after combining amplified ICD with CTLA4 checkpoint blockade. The 21-day primary and distant tumor inhibition rates reached 90%, and the underlying mechanism of the effective synergetic strategy of inducing the T-cell-related response, the immune memory effect and TIME reprogramming in vivo was verified by immune cell analyses. This remarkable therapeutic effect provides a new direction for antitumor immunotherapy based on magnetothermally controlled oxygen-independent free radical release.

Details

Language :
English
ISSN :
25900064
Volume :
16
Issue :
100442-
Database :
Directory of Open Access Journals
Journal :
Materials Today Bio
Publication Type :
Academic Journal
Accession number :
edsdoj.2769c133f2ca4dc68ea9ff7f3bdb0d2a
Document Type :
article
Full Text :
https://doi.org/10.1016/j.mtbio.2022.100442