Chemo-photodynamic therapy with light-triggered disassembly of theranostic nanoplatform in combination with checkpoint blockade for immunotherapy of hepatocellular carcinoma.
Chemo-photodynamic therapy with light-triggered disassembly of theranostic nanoplatform in combination with checkpoint blockade for immunotherapy of hepatocellular carcinoma.
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光触发治疗诊断纳米平台拆卸结合检查点阻断的化学光动力疗法用于肝细胞癌的免疫治疗
DOI：
10.1186/s12951-021-01101-1
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发表时间：
2021-10-30
影响因子：
10.2
通讯作者：
Gao Y
中科院分区：
文献类型：
--
作者：
Xu J;Zheng Q;Cheng X;Hu S;Zhang C;Zhou X;Sun P;Wang W;Su Z;Zou T;Song Z;Xia Y;Yi X;Gao Y
肝细胞癌（Hepatocellular carcinoma，HCC）是一种常见的恶性肿瘤，具有高转移率和高复发率.尽管免疫检查点阻断（ICB）已成为晚期HCC中一种有前途的免疫疗法，但单独使用ICB治疗的客观缓解率低于20%。因此，需要联合治疗策略来提高治疗反应率和治疗效果。方法制备了一种共负载聚集诱导发射（AIE）光敏剂（TB）和紫杉醇（PTX）的光触发拆卸纳米平台（TB/PTX@RTK），用于按指令药物释放和协同化学光动力学治疗（chemo-photodynamic therapy，chemo-PDT）。纳米胶束的载药含量，流体动力学尺寸，吸收和发射光谱，活性氧的生产，以及从胶束中释放的PTX进行了表征。结果TB/PTX @ RTK胶束可通过cRGD介导的活性靶点在肿瘤部位特异性聚集，促进图像引导PDT治疗肿瘤。一旦受到光照射，TB的AIE光敏剂即可产生用于PDT的活性氧，硫缩酮接头可被活性氧切割，从而在肿瘤细胞中精确释放紫杉醇。化疗-PDT不仅可以协同抑制肿瘤生长，而且可以诱导免疫原性细胞死亡，引发抗肿瘤免疫应答。同时，化疗光动力疗法可显著上调肿瘤细胞表面PD-L1的表达，与抗PD-L1单克隆抗体协同诱导远端效应，结论TB/PTX@RTK胶束介导的化学光动力疗法与抗PD-L1单克隆抗体的联合应用可协同增强全身抗PD-L1抗体的作用，并可有效抑制肿瘤的复发和转移。肿瘤作用，并提供了一个新的见解，以发展新的纳米药物与精确控制释放和多模式治疗，以提高肝癌的治疗效果。图形摘要
BackgroundHepatocellular 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.MethodsA 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.ResultsThe 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.ConclusionOur 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.Graphical Abstract
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DOI：
10.3322/caac.20114
发表时间：
2011-07
期刊：
CA: a cancer journal for clinicians
影响因子：
--
作者：
Agostinis P;Berg K;Cengel KA;Foster TH;Girotti AW;Gollnick SO;Hahn SM;Hamblin MR;Juzeniene A;Kessel D;Korbelik M;Moan J;Mroz P;Nowis D;Piette J;Wilson BC;Golab J
通讯作者：
Golab J
影响因子：
10.2
作者：
Bahreyni A;Mohamud Y;Luo H
通讯作者：
Luo H
影响因子：
14
作者：
Li, Xingshu;Jeon, Yun-Hui;Yoon, Juyoung
通讯作者：
Yoon, Juyoung
DOI：
10.1158/1078-0432.ccr-17-0186
发表时间：
2018-02-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
O'Shaughnessy MJ;Murray KS;La Rosa SP;Budhu S;Merghoub T;Somma A;Monette S;Kim K;Corradi RB;Scherz A;Coleman JA
通讯作者：
Coleman JA
温和的光热疗法通过一体化和全控策略增强免疫冷肿瘤的抗 PD-L1 治疗
影响因子：
16.6
作者：
Huang, Liping;Li, Yanan;Sun, Chunmeng
通讯作者：
Sun, Chunmeng