Chemical Modulation of Glucose Metabolism with a Fluorinated CaCO3 Nanoregulator Can Potentiate Radiotherapy by Programming Antitumor Immunity

被引:64
作者
Dong, Ziliang [1 ]
Wang, Chunjie [2 ]
Gong, Yimou [2 ]
Zhang, Yunyun [2 ]
Fan, Qin [2 ]
Hao, Yu [2 ]
Li, Quguang [2 ]
Wu, Yumin [2 ]
Zhong, Xiaoyan [3 ,4 ]
Yang, Kai [3 ,4 ]
Feng, Liangzhu [2 ]
Liu, Zhuang [2 ]
机构
[1] Shanghai Jiao Tong Univ, Renji Hosp, Inst Mol Med, Sch Med, Shanghai 200127, Peoples R China
[2] Soochow Univ, Inst Funct Nano & Soft Mat FUNSOM, Jiangsu Key Lab Carbon Based Funct Mat & Devices, Suzhou 215123, Jiangsu, Peoples R China
[3] Soochow Univ, Collaborat Innovat Ctr Radiat Med Jiangsu Higher E, Sch Radiat Med & Protect, State Key Lab Radiat Med & Protect, Suzhou 215123, Jiangsu, Peoples R China
[4] Soochow Univ, Collaborat Innovat Ctr Radiat Med Jiangsu Higher E, Sch Radiol & Interdisciplinary Sci RADX, Suzhou 215123, Jiangsu, Peoples R China
基金
中国博士后科学基金; 中国国家自然科学基金;
关键词
fluorinated CaCO3 nanoregulator; glucose metabolism modulation; acidity neutralization; hypoxia attenuation; enhanced radiotherapy; antitumor immunity; TUMOR MICROENVIRONMENT; CANCER; HYPOXIA; NANOPARTICLES; THERAPY; RESISTANCE;
D O I
10.1021/acsnano.2c02688
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
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.
引用
收藏
页码:13884 / 13899
页数:16
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