期刊
ACS NANO
卷 16, 期 3, 页码 3881-3894出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsnano.1c09048
关键词
nitric oxide; immunogenic cell death; NO nanogenerator; vaccination effects; PD-1 blockade therapy
类别
资金
- National Key R&D Program of China [2020YFA0710700]
- National Natural Science Foundation of China [52025036, 51903105, 51961145109]
- Fundamental Research Fund for the Central Universities [WK9100000014, WK2480000006]
- Project of Collaborative Innovation for Colleges of Anhui Province [GXXT-2021-070]
The study shows that the gaseous molecule nitric oxide (NO) can induce immunogenic cell death (ICD) in tumor cells, triggering a protective immune response.
Tumor cells undergoing immunogenic cell death (ICD) release immunogenic damage-associated molecular patterns (DAMPs) to trigger a long-term protective antitumor response. ICD can be induced by certain pathogens, chemotherapeutics, and physical modalities. In this work, we demonstrate that a gaseous molecule, specifically nitric oxide (NO), can induce a potent ICD effect. NO exerts cytotoxic effects that are accompanied by the emission of DAMPs based on the endoplasmic reticulum stress and mitochondrial dysfunction pathways. Released DAMPs elicit immunological protection against a subsequent rechallenge of syngeneic tumor cells in immunocompetent mice. We prepare polynitrosated polyesters with high NO storage capacity through a facile polycondensation reaction followed by a postsynthetic modification. The polynitrosated polyesters-based NO nanogenerator (NanoNO) that enables efficient NO delivery and controlled NO release in tumors induces a sufficient ICD effect. In different immune-intact models of tumors, the NanoNO exhibits significant tumor growth suppression and increases the local dose of immunogenic signals and T cell infiltrations, ultimately prolonging survival. In addition, the NanoNO synergizes with the PD-1 blockade to prevent metastasis. We conclude not only that NO is a potent ICD inducer for cancer immunotherapy but also that it expands the range of ICD inducers into the field of gaseous molecules.
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