The integration of nanomedicine and immunotherapy has presented a promising opportunity for the treatment of cancer and diverse diseases. However, achieving spatiotemporal controllable immunotherapy with excellent efficacy and safety performances remains a significant challenge. This study develops a biodegradable near-infrared II (NIR-II) photothermal response polymer nanoparticle (PTEQ) system. This platform exhibits intrinsic immunostimulatory properties while concurrently delivering siRNA for Programmed Death-Ligand 1 (siPD-L1), leveraging enhanced immune responses and immune checkpoint blockade for safe and effective cancer therapy. In the CT26 tumor-bearing mouse model, PTEQ, as an immune stimulant, significantly boosts the infiltration of CD4⁺ and CD8⁺ T cells within the tumor microenvironment (TME). The PTEQ/siPD-L1+laser group not only initiates NIR-II photothermal therapy but also promotes the activation and infiltration of T cells, M1 macrophage polarization, and maturation of dendritic cells in the TME, resulting in the complete elimination of tumors in 7/10 cases, achieving a 100% survival rate. In another in vivo vaccine experiment, all tumors on the right side are completely eliminated in the PTEQ/siPD-L1+laser group, reaching a 100% tumor eradication rate. These findings underscore the potential of this strategy to overcome the current immunotherapeutic limitations and achieve immune therapy normalization.

中文翻译：

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时空控制的 NIR-II 免疫激动剂使癌症免疫疗法变得敏感

纳米医学和免疫疗法的结合为癌症和多种疾病的治疗提供了充满希望的机会。然而，实现具有优异疗效和安全性能的时空可控免疫治疗仍然是一个重大挑战。本研究开发了一种可生物降解的近红外 II (NIR-II) 光热响应聚合物纳米颗粒 (PTEQ) 系统。该平台具有内在的免疫刺激特性，同时为程序性死亡配体 1 (siPD-L1) 提供 siRNA，利用增强的免疫反应和免疫检查点阻断来实现安全有效的癌症治疗。在 CT26 荷瘤小鼠模型中，PTEQ 作为一种免疫刺激剂，可显着促进肿瘤微环境 (TME) 内 CD4 ⁺和 CD8 ⁺ T 细胞的浸润。 PTEQ/siPD-L1+激光组不仅启动NIR-II光热治疗，还促进TME中T细胞的活化和浸润、M1巨噬细胞极化以及树突状细胞的成熟，从而在7年内彻底消除肿瘤/10例，达到100%的存活率。在另一项体内疫苗实验中，PTEQ/siPD-L1+激光组右侧所有肿瘤被完全消除，达到100%的肿瘤根除率。这些发现强调了该策略克服当前免疫治疗局限性并实现免疫治疗正常化的潜力。