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Chemo-photodynamic therapy with light-triggered disassembly of theranostic nanoplatform in combination with checkpoint blockade for immunotherapy of hepatocellular carcinoma

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单位: [1]Huazhong Univ Sci & Technol, Union Hosp, Tongji Med Coll, Dept Hepatobiliary Surg, Wuhan 430022, Peoples R China [2]Huazhong Univ Sci & Technol,Tongji Hosp,Tongji Med Coll,Dept Gen Surg,Wuhan 430030,Peoples R China [3]Gannan Med Univ, Coll Pharm,Minist Educ, Key Lab Prevent & Treatment Cardiovasc & Cerebrov, Key Lab Biomat & Biofabricat Tissue Engn Jiangxi, Ganzhou 341000, Peoples R China
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关键词: Theranostic nanoplatform Aggregation-induced emission (AIE) Light-triggered nanomedicine Cancer immunotherapy Immune checkpoint blockade Photodynamic therapy Chemotherapy

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Background: Hepatocellular carcinoma (HCC) is a common malignant tumor with high rate of metastasis and recurrence. Although immune checkpoint blockade (ICB) has emerged as a promising type of immunotherapy in advanced HCC, treatment with ICB alone achieves an objective remission rate less than 20%. Thus, combination therapy strategies is needed to improve the treatment response rate and therapeutic effect. Methods: A light-triggered disassembly of nanoplatform (TB/PTX@RTK) co-loaded an aggregation induced emission (AIE) photosensitizer (TB) and paclitaxel (PTX) was prepared for on-command drug release and synergistic chemo-photodynamic therapy (chemo-PDT). Nano-micelles were characterized for drug loading content, hydrodynamic size, absorption and emission spectra, reactive oxygen species production, and PTX release from micelles. The targeted fluorescence imaging of TB/PTX@RTK micelles and the synergistic anti-tumor efficacy of TB/PTX@RTK micelles-mediated chemo-PDT combined with anti-PD-L1 were assessed both in vitro and in vivo. Results: The TB/PTX@RTK micelles could specifically accumulate at the tumor site through cRGD-mediated active target and facilitate image-guided PDT for tumor ablation. Once irradiated by light, the AIE photosensitizer of TB could produce ROS for PDT, and the thioketal linker could be cleaved by ROS to precise release of PTX in tumor cells. Chemo-PDT could not only synergistically inhibit tumor growth, but also induce immunogenic cell death and elicit anti-tumor immune response. Meanwhile, chemo-PDT significantly upregulated the expression of PD-L1 on tumor cell surface which could efficiently synergize with anti-PD-L1 monoclonal antibodies to induce an abscopal effect, and establish long-term immunological memory to inhibit tumor relapse and metastasis. Conclusion: Our results suggest that the combination of TB/PTX@RTK micelle-mediated chemo-PDT with anti-PD-L1 monoclonal antibodies can synergistically enhance systemic anti-tumor effects, and provide a novel insight into the development of new nanomedicine with precise controlled release and multimodal therapy to enhance the therapeutic efficacy of HCC.

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出版当年[2020]版:
大类 | 2 区 工程技术
小类 | 2 区 生物工程与应用微生物 3 区 纳米科技
最新[2025]版:
大类 | 1 区 生物学
小类 | 1 区 生物工程与应用微生物 2 区 纳米科技
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出版当年[2019]版:
Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Q2 NANOSCIENCE & NANOTECHNOLOGY
最新[2023]版:
Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Q1 NANOSCIENCE & NANOTECHNOLOGY

影响因子: 最新[2023版] 最新五年平均 出版当年[2019版] 出版当年五年平均 出版前一年[2018版] 出版后一年[2020版]

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第一作者单位: [1]Huazhong Univ Sci & Technol, Union Hosp, Tongji Med Coll, Dept Hepatobiliary Surg, Wuhan 430022, Peoples R China
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