Rationally Designed Polymer Conjugate for Tumor-Specific Amplification of Oxidative Stress and Boosting Antitumor Immunity

The crosstalk between tumor and stroma cells is a central scenario in the tumor microenvironment (TME). While the predominant effect of tumor cells on immune cells is establishing an immunosuppressive context, tumor cell death at certain conditions will boost antitumor immunity. Herein, we report a...

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Bibliographic Details
Published in:Nano letters 2020-04, Vol.20 (4), p.2514-2521
Main Authors: Ma, Sheng, Song, Wantong, Xu, Yudi, Si, Xinghui, Lv, Shixian, Zhang, Yu, Tang, Zhaohui, Chen, Xuesi
Format: Article
Language:English
Subjects:
Acrolein - analogs & derivatives
Acrolein - chemistry
Acrolein - pharmacology
Animals
Antineoplastic Agents - chemistry
Antineoplastic Agents - pharmacology
Cell Line, Tumor
Humans
Immunity - drug effects
Immunotherapy
Mice
Neoplasms - drug therapy
Neoplasms - immunology
Neoplasms - metabolism
Oxidative Stress - drug effects
Polyethylene Glycols - chemistry
Polyethylene Glycols - pharmacology
Polyglutamic Acid - analogs & derivatives
Polyglutamic Acid - pharmacology
Polymers - chemistry
Polymers - pharmacology
Tumor Microenvironment - drug effects
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Summary:The crosstalk between tumor and stroma cells is a central scenario in the tumor microenvironment (TME). While the predominant effect of tumor cells on immune cells is establishing an immunosuppressive context, tumor cell death at certain conditions will boost antitumor immunity. Herein, we report a rationally designed tumor specific enhanced oxidative stress polymer conjugate (TSEOP) for boosting antitumor immunity. The TSEOP is prepared by Passerini reaction between cinnamaldehyde (CA), 4-formylbenzene­boronic acid pinacol ester, and 5-isocyanopent-1-yne, followed by azide–alkyne click reaction with poly­(l-glutamic acid)-graft-poly­(ethylene glycol) monomethyl ether (PLG-g-mPEG). Under tumor stimuli condition, CA and quinone methide (QM) are quickly generated, which cooperatively induce strong oxidative stress, immunogenic tumor cell death (ICD), and activation of antigen presenting cells. In vivo studies show that the TSEOP treatment boosts tumor-specific antitumor immunity and eradicates both murine colorectal and breast tumors. This study should be inspirational for designing polymers as immunotherapeutics in cancer therapy.
ISSN:1530-6984
1530-6992
DOI:10.1021/acs.nanolett.9b05265