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

作　　者：Yunyun Zhang Ziliang Dong Yu Hao Yimou Gong Chunjie Wang Yifan Yan Minming Chen Yumin Wu Quguang Li Zhuang Liu Liangzhu Feng 

机构地区：[1]Institute of Functional Nano&Soft Materials(FUNSOM),Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices,Soochow University,199 Ren’ai Road,Suzhou 215123,China

出　　处：《Nano Research》2023年第7期9815-9825,共11页纳米研究（英文版）

基　　金：This work was partially supported by the National Natural Science Foundation of China(No.22077093);the National Research Programs from Ministry of Science and Technology(MOST)of China(Nos.2021YFF0701800 and 2022YFF0706500);the Natural Science Foundation of Jiangsu Province(No.BK20220110);the Collaborative Innovation Center of Suzhou Nano Science and Technology,the Suzhou Key Laboratory of Nanotechnology and Biomedicine,and the 111 Program from the Ministry of Education of China。

摘　　要：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 

分 类 号：R730.51[医药卫生—肿瘤]