期刊
ACS NANO
卷 -, 期 -, 页码 -出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsnano.2c02688
关键词
fluorinated CaCO3 nanoregulator; glucose metabolism modulation; acidity neutralization; hypoxia attenuation; enhanced radiotherapy; antitumor immunity
类别
资金
- National Natural Science Foundation of China [22077093, 52032008]
- Ministry of Science and Technology (MOST) of China [2021YFF0701800]
- Natural Science Foundation of Jiangsu Province [BK20220110]
- Jiangsu Social Development Project [BE2019658]
- China Postdoctoral Science Foundation [2021M700089]
- Collaborative Innovation Center of Suzhou Nano Science and Technology
- Suzhou Key Laboratory of Nanotechnology and Biomedicine
- 111 Program from the Ministry of Education of China
This study presents the preparation of a multifunctional fluorinated calcium carbonate nanoregulator that can reverse tumor immunosuppression and potentiate radiotherapy by chemically modulating tumor hypoxic and acidic microenvironments.
Tumor hypoxia and acidity are well-known features in solid tumors that cause immunosuppression and therapeutic resistance. Herein, we rationally synthesized a multifunctional fluorinated calcium carbonate (fCaCO(3)) nanoregulator by coating CaCO3 nanoparticles with dopamine-grafted perfluorosebacic acid (DA(2)-PFSEA) and ferric ions by utilizing their coordination interaction. After PEGylation, the obtained fCaCO(3)-PEG showed high loading efficacy to perfluoro-15-crown-5-ether (PFCE), a type of perfluorocarbon with high oxygen solubility, thereby working as both oxygen nanoshuttles and proton sponges to reverse tumor hypoxia and acidity-induced resistance to radiotherapy. The as-prepared PFCE@fCaCO(3)-PEG could not only function as long-circulating oxygen nanoshuttles to attenuate tumor hypoxia but also neutralize the acidic tumor microenvironment by restricting the production of lactic acid and reacting with extracellular protons. As a result, treatment with PFCE@fCaCO(3)-PEG could improve the therapeutic outcome of radiotherapy toward two murine tumors with distinct immunogenicity. The PFCE@ fCaCO(3)-PEG-assisted radiotherapy could also collectively inhibit the growth of unirradiated tumors and reject rechallenged tumors by synergistically eliciting protective antitumor immunity. Therefore, our work presents the preparation of fluorinated CaCO3 nanoregulators to reverse tumor immunosuppression and potentiate radiotherapy through chemically modulating tumor hypoxic and acidic microenvironments tightly associated with tumor glucose metabolism.
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