期刊
ADVANCED MATERIALS
卷 33, 期 20, 页码 -出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/adma.202008065
关键词
innate immune; M1 polarization; nanoplatform; ox‐ mtDNA
类别
资金
- National Natural Science Foundation of China [52 072 394, 21 835 007]
- Shanghai Science and Technology Committee Rising-Star Program [19QA1410100]
- Youth Innovation Promotion Association of the Chinese Academy of Science [SHDSYY-2018-Z0026]
A novel tumor immunotherapy modality based on nanocatalytic innate immunity activation by inducing oxidative damage in tumor cells' mtDNA is proposed. This approach reactivates macrophages' immune response against cancer cells, leading to the inhibition of primary and distant tumor growth during treatment.
The innate immune system plays a key role in protecting the human body from tumors, which, unfortunately, is largely counteracted by their immune-suppression function. Such an immune suppression has been reported to be induced by the immunosuppressive microenvironment, including the exhausted cytotoxic T lymphocytes (CTLs) and tumor-promoting M2-polarized macrophages. Here, a novel tumor-immunotherapeutic modality based on the nanocatalytic innate immunity activation by tumor-specific mitochondrial DNA (mtDNA) oxidative damage is proposed. In detail, a nanocatalytic medicine, Fe2+-Ru2+-loaded mesoporous silica nanoparticle named as MSN-Ru2+/Fe2+ (MRF), is constructed to induce oxidative damage in the mtDNA of tumor cells. Such an oxidative mtDNA is able to escape from the tumor cells and acts as an immunogenic damage-associated molecular pattern to M1-polarize tumor-associated macrophages (TAMs), resulting in the reactivated immunoresponse of macrophages against cancer cells, and the subsequent inflammatory response of innate immunity. Most importantly, the treatment strategy based on regulating the innate immune response of TAMs not only stops the primary tumor progression, but also almost completely inhibits the growth of distant tumors in the periods of treatments.
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