Surface-Functionalized Modified Copper Sulfide Nanoparticles Enhance Checkpoint Blockade Tumor Immunotherapy by Photothermal Therapy and Antigen Capturing
Surface-Functionalized Modified Copper Sulfide Nanoparticles Enhance Checkpoint Blockade Tumor Immunotherapy by Photothermal Therapy and Antigen Capturing
复制标题
表面功能化修饰的硫化铜纳米粒子通过光热疗法和抗原捕获增强检查点阻断肿瘤免疫治疗
DOI：
10.1021/acsami.9b01107
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发表时间：
2019-04-17
影响因子：
9.5
通讯作者：
Gao, Fuping
中科院分区：
文献类型：
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作者：
Wang, Ruoping;He, Zhesheng;Gao, Fuping
基于纳米材料的肿瘤光热疗法（PTT）因其不良反应低且无创性而受到越来越多的关注，并且成为一种有前途的癌症治疗方法。然而，单纯热疗仍无法控制肿瘤转移和复发。在这里，我们开发了表面功能化改性的硫化铜纳米颗粒（CuS NP）。 CuS NPs不仅可以用作肿瘤热疗的光热介质，还可以吸附热疗过程中释放的肿瘤抗原作为抗原捕获剂，诱导抗肿瘤免疫反应。我们选择了具有更强抗原吸附能力的马来酰亚胺聚乙二醇修饰的CuS NPs（CuS NPs-PEG-Mal），与免疫检查点阻断剂（抗PD-L1）联合评估热疗效果，改善4T1乳腺癌肿瘤模型的免疫治疗。结果表明，基于 CuS NPs-PEG-Mal 的热疗明显增加了血清中炎症细胞因子的水平，导致肿瘤免疫原性微环境。与抗 PD-L1 配合，CuS NPs-PEG-Mal 介导的 PTT 增加了肿瘤浸润 CDR+ T 细胞的数量，并抑制了 4T1 肿瘤模型中原发和远处肿瘤部位的生长。该治疗策略为转移性和复发性肿瘤提供了简单有效的治疗选择。
Nanomaterial-based tumor photothermal therapy (PTT) has attracted increasing attention and been a promising method for cancer treatment because of its low level of adverse effects and noninvasiveness. However, thermotherapy alone still cannot control tumor metastasis and recurrence. Here, we developed surface-functionalized modified copper sulfide nanoparticles (CuS NPs). CuS NPs can not only be used as photothermal mediators for tumor hyperthermia but can adsorb tumor antigens released during hyperthermia as an antigen-capturing agent to induce antitumor immune response. We selected maleimide polyethylene glycol-modified CuS NPs (CuS NPs-PEG-Mal) with stronger antigen adsorption capacity, in combination with an immune checkpoint blocker (anti-PD-L1) to evaluate the effect of hyperthermia, improving immunotherapy in a 4T1 breast cancer tumor model. The results showed that hyperthermia based on CuS NPs-PEG-Mal distinctly increased the levels of inflammatory cytokines in the serum, leading to a tumor immunogenic microenvironment. In cooperation with anti-PD-L1, PTT mediated by CuS NPs-PEG-Mal enhanced the number of tumor-infiltrating CDR+ T cells and inhibited the growth in primary and distant tumor sites of the 4T1 tumor model. The therapeutic strategies provide a simple and effective treatment option for metastatic and recurrent tumors.