School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore, Singapore.
Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore, Singapore.
Nat Commun. 2021 Feb 2;12(1):742. doi: 10.1038/s41467-021-21047-0.
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.
纳米医学与免疫疗法相结合，为安全有效地治疗癌症提供了机会；然而，如何实现具有时空精准性的免疫反应远程控制仍然具有挑战性。本文报道了一种光热激活型聚合物前纳米激动剂（APNA），它可通过组织穿透性深的第二近红外（NIR-II）光来特异性调控，用于联合光热免疫治疗。APNA 通过将免疫刺激剂共价连接到 NIR-II 半导体换能器上，通过不稳定的热响应连接体构建而成。在近红外 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，还引发热不稳定连接体的裂解，释放出笼状激动剂，在深部实体肿瘤（8mm）中进行原位免疫激活。这种受控的免疫调节增强了系统抗肿瘤免疫力，导致在远端肿瘤、肺和肝脏中促进细胞毒性 T 淋巴细胞和辅助性 T 细胞浸润，从而抑制癌症转移。因此，本工作说明了一种用于癌症纳米免疫治疗时空调控的前免疫刺激剂的通用制备策略。
