Activatable polymer nanoagonist for second near-infrared photothermal immunotherapy of cancer.
Activatable polymer nanoagonist for second near-infrared photothermal immunotherapy of cancer.
复制标题
用于癌症第二次近红外光热免疫治疗的可活化聚合物纳米激动剂。
DOI：
10.1038/s41467-021-21047-0
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发表时间：
2021-02-02
影响因子：
16.6
通讯作者：
Pu K
中科院分区：
文献类型：
--
作者：
Jiang Y;Huang J;Xu C;Pu K
纳米医学与免疫疗法相结合，为以安全有效的方式治疗癌症提供了机会；然而，以时空精确度远程控制免疫反应仍然具有挑战性。在此，我们报道了一种光热可激活的聚合物前纳米激动剂(APNA)，它受深组织穿透第二近红外(NIR-II)光的特异性调节，用于组合光热免疫治疗。APNA是通过不稳定的热反应接头将免疫刺激剂共价连接到NIR-II半导体传感器上而构建的。在NIR-II光照射下，APNA介导光热效应，不仅触发肿瘤消融和免疫原性细胞死亡，还启动不耐热连接蛋白的裂解，释放笼子中的激动剂，用于在深部实体瘤(8 mm)的原位免疫激活。这种受控的免疫调节增强了系统的抗肿瘤免疫，导致促进了细胞毒性T淋巴细胞和辅助T细胞在远端肿瘤、肺和肝脏的渗透，从而抑制了肿瘤的转移。因此，本工作阐明了制备用于肿瘤纳米免疫治疗时空调节的前免疫刺激剂的通用策略。对于癌症免疫治疗来说，精确控制免疫反应仍然是一个挑战。在这里，作者报告了光热可激活的半导体聚合物激动剂响应第二近红外窗口光调节光热免疫治疗。
Nanomedicine in combination with immunotherapy offers opportunities to treat cancer in a safe and effective manner; however, remote control of immune response with spatiotemporal precision remains challenging. We herein report a photothermally activatable polymeric pro-nanoagonist (APNA) that is specifically regulated by deep-tissue-penetrating second near-infrared (NIR-II) light for combinational photothermal immunotherapy. APNA is constructed from covalent conjugation of an immunostimulant onto a NIR-II semiconducting transducer through a labile thermo-responsive linker. Upon NIR-II photoirradiation, APNA mediates photothermal effect, which not only triggers tumor ablation and immunogenic cell death but also initiates the cleavage of thermolabile linker to liberate caged agonist for in-situ immune activation in deep solid tumor (8 mm). Such controlled immune regulation potentiates systemic antitumor immunity, leading to promoted cytotoxic T lymphocytes and helper T cell infiltration in distal tumor, lung and liver to inhibit cancer metastasis. Thereby, the present work illustrates a generic strategy to prepare pro-immunostimulants for spatiotemporal regulation of cancer nano-immunotherapy. Precise control of immune response remains challenging for cancer immunotherapy. Here, the authors report on photothermally activatable semiconducting polymeric pro-agonist in response to second near-infrared window light for regulated photothermal immunotherapy.
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影响因子：
14
作者：
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通讯作者：
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作者：
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