Journal
NANO LETTERS
Volume 20, Issue 4, Pages 2514-2521Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.nanolett.9b05265
Keywords
Polypeptide; oxidative stress; immunogenic cell death; immunotherapy
Categories
Funding
- National Natural Science Foundation of China [51673185, 51973215, 51673189, 51833010, 51520105004, 51829302]
- Jilin Province Science and Technology Development Plan [20190103112JH]
- Ministry of Science and Technology of China [2016YFC1100701]
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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.
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