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A tumor microenvironment responsive biodegradable CaCO3/MnO2- based nanoplatform for the enhanced photodynamic therapy and improved PD-L1 immunotherapy

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机构: [1]Shanghai Jiao Tong Univ, Shanghai Engn Res Ctr Intelligent Diag & Treatmen, Dept Instrument Sci & Engn, Sch Elect Informat & Elect Engn,Inst Nano Biomed, 800 Dongchuan Rd, Shanghai 200240, Peoples R China [2]Shanghai Jiao Tong Univ, Natl Ctr Translat Med, Collaborat Innovat Ctr Syst Biol, Shanghai 200240, Peoples R China [3]Shanghai Jiao Tong Univ, Tongren Hosp, Sch Med, 1111 XianXia Rd, Shanghai 200336, Peoples R China
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关键词: MnO2 Photodynamic therapy PD-L1 Tumor immunotherapy

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The low efficiency of photodynamic therapy (PDT) is caused by tumor hypoxia and the adaptive immune resistance/evasion of tumor cells, while the currently emerging immune checkpoint therapy restores the intrinsic immune capacities but can't directly attack the tumor cells. Methods: Herein we report an integrated nanoplatform that combines PDT with immunotherapy to enhance photodynamic therapeutic effects and simultaneously inhibit tumor cells resistance/evasion. To achieve this, we fabricated Mn@CaCO3/ICG nanoparticles and loaded them with PD-L1-targeting siRNA. Results: Thanks to the protection of CaCO3 on the loaded ICG and the oxygen produced by MnO2, an enhanced photodynamic therapeutic effect in vitro was observed. In vivo experiments demonstrated that the nanoplatform could efficiently deliver the loaded drug to the tumor tissues and significantly improve tumor hypoxia, which further contributes to the therapeutic effect of PDT in vivo. Moreover, the synergistic benefits derived from the siRNA, which silenced the checkpoint gene PD-L1 that mediates the immune resistance/evasion, resulted in a surprising therapeutic effect to rouse the immune system. Conclusions: The combination treatment strategy has great potential to be developed as a new and robust method for enhanced PDT therapy with high efficiency and a powerful antitumor immune response based on PD-L1 blockade.

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出版当年[2018]版:
大类 | 1 区 医学
小类 | 1 区 医学:研究与实验
最新[2023]版:
大类 | 1 区 医学
小类 | 1 区 医学:研究与实验
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出版当年[2017]版:
Q1 MEDICINE, RESEARCH & EXPERIMENTAL
最新[2023]版:
Q1 MEDICINE, RESEARCH & EXPERIMENTAL

影响因子: 最新[2023版] 最新五年平均 出版当年[2017版] 出版当年五年平均 出版前一年[2016版] 出版后一年[2018版]

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第一作者机构: [1]Shanghai Jiao Tong Univ, Shanghai Engn Res Ctr Intelligent Diag & Treatmen, Dept Instrument Sci & Engn, Sch Elect Informat & Elect Engn,Inst Nano Biomed, 800 Dongchuan Rd, Shanghai 200240, Peoples R China [2]Shanghai Jiao Tong Univ, Natl Ctr Translat Med, Collaborat Innovat Ctr Syst Biol, Shanghai 200240, Peoples R China
通讯作者:
通讯机构: [1]Shanghai Jiao Tong Univ, Shanghai Engn Res Ctr Intelligent Diag & Treatmen, Dept Instrument Sci & Engn, Sch Elect Informat & Elect Engn,Inst Nano Biomed, 800 Dongchuan Rd, Shanghai 200240, Peoples R China [2]Shanghai Jiao Tong Univ, Natl Ctr Translat Med, Collaborat Innovat Ctr Syst Biol, Shanghai 200240, Peoples R China
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