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Synthesis of fluorinated CaCO_(3)-based oxygen-supplying nanophotosensitizers to potentiate photodynamic immunotherapy by reversing tumor hypoxia and immunosuppression

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Nano Research 2023年第7期16卷 9815-9825页

作者： Yunyun Zhang Ziliang Dong Yu Hao Yimou Gong Chunjie Wang Yifan Yan Minming Chen Yumin Wu Quguang Li Zhuang Liu Liangzhu Feng Institute of Functional Nano&Soft Materials(FUNSOM) Jiangsu Key Laboratory for Carbon-Based Functional Materials and DevicesSoochow University199 Ren’ai RoadSuzhou 215123China

Photodynamic therapy is a noninvasive type of phototherapy with a high capacity to boost specific antitumor immunity by causing immunogenic cell death.However,the photodynamic therapeutic potency toward solid tumors is dampened by tumor hypoxia that negatively impairs the generation of cytotoxic singlet oxygen and promotes the formation of tumor immunosuppression.Herein,fluorinated CaCO_(3)(CaF)nanoparticles are prepared with the addition of dopamine-conjugated perfluorosebacic acid and ferric chloride into a calcium chloride ethanol solution via an ammonium bicarbonate-mediated gas-diffusion process.After being coated with commercial lipids and hexadecylamin conjugated chlorin e6(hCe6)via a templated self-assembly process,the yielded PEGylated nanophotosensitizer(hCe6@CaF-PEG)exhibits an effective loading efficiency to perfluoro-15-crown-5-ether(PFCE),a model perfluorocarbon molecule,and thus oxygen molecules.Upon intravenous administration,the obtained PFCE/hCe6@CaF-PEG can alleviate tumor hypoxia by working as an oxygen nanoshuttle.Together with local light emitting diode light exposure,photodynamic treatment with PFCE/hCe6@CaF-PEG can suppress the growth of primary CT26 tumors and unirradiated distant tumors,particularly when synergized with anti-PD-1(aPD-1)immunotherapy to collectively reverse tumor immunosuppression.This work presents an effective strategy to potentiate photodynamic immunotherapy by concurrently reversing tumor hypoxia and immunosuppression.

关键词： photodynamic immunotherapy fluorinated CaCO_(3)nanoparticles oxygen-supplying nanophotosensitizer tumor hypoxia attenuation reversal of tumor immunosuppression

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