期刊
ACS NANO
卷 13, 期 8, 页码 8811-8825出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsnano.9b01979
关键词
ferrimagnetic vortex-domain iron oxide nanorings; mild magnetic hyperthermia; PD-L1 blockade immunotherapy; immunological effect; cancer metastasis
类别
资金
- Natural Science Foundation [31630027, 31430031]
- NSFC-DFG [31761133013]
- Ministry of Science and Technology of China [2017YFA0205200]
- CAS [XDA09030301]
- National Natural Science Foundation of China [81571809, 81771981, 81871514, 81470083, 81227901]
Cancer metastasis is a serious concern and a major reason for treatment failure. Herein, we have reported the development of an effective and safe nanotherapeutic strategy that can eradicate primary tumors, inhibit metastasizing to lung, and control the metastasis and growth of distant tumors. Briefly, ferrimagnetic vortex-domain iron oxide nanoring (FVIO)-mediated mild magnetic hyperthermia caused calreticulin (CRT) expression on the 4T1 breast cancer cells. The CRT expression transmitted an eat-me signal and promoted phagocytic uptake of cancer cells by the immune system to induce an efficient immunogenic cell death, further leading to the macrophage polarization. This mild thermotherapy promoted 88% increase of CD8(+) cytotoxic T lymphocyte infiltration in distant tumors and triggered immunotherapy by effectively sensitizing tumors to the PD-L1 checkpoint blockade. The percentage of CD8(+) cytotoxic T lymphocytes can be further increased from 55.4% to 64.5% after combining with PD-L1 blockade. Moreover, the combination treatment also inhibited the immunosuppressive response of the tumor, evidenced by significant down-regulation of myeloid-derived suppressor cells (MDSCs). Our results revealed that the FWD-mediated mild magnetic hyperthermia can activate the host immune systems and efficiently cooperate with PD-L1 blockade to inhibit the potential metastatic spreading as well as the growth of distant tumors.
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