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时空可控近红外二区免疫激动剂敏化癌症免疫治疗。

Spatiotemporal-Controlled NIR-II Immune Agonist Sensitizes Cancer Immunotherapy.

机构信息

Advanced Research Institute of Multidisciplinary Science, School of Life Science, Key Laboratory of Molecular Medicine and Biotherapy, Key Laboratory of Medical Molecule Science and Pharmaceutics Engineering, Beijing Institute of Technology, Beijing, 100081, China.

Beijing National Laboratory for Molecular Sciences Laboratory of Polymer Physics and Chemistry Institute of Chemistry, Chinese Academy of Sciences, Beijing, 100190, P. R. China.

出版信息

Adv Mater. 2024 Jun;36(25):e2400228. doi: 10.1002/adma.202400228. Epub 2024 Mar 21.

Abstract

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.

摘要

纳米医学和免疫疗法的融合为癌症和多种疾病的治疗提供了一个有前途的机会。然而,实现具有优异疗效和安全性的时空可控免疫疗法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粒子(PTEQ)系统。该平台具有内在的免疫刺激特性,同时递送程序性死亡配体 1(siPD-L1)的 siRNA,利用增强的免疫反应和免疫检查点阻断来进行安全有效的癌症治疗。在 CT26 荷瘤小鼠模型中,PTEQ 作为免疫刺激物,显著增加了肿瘤微环境(TME)中 CD4 和 CD8 T 细胞的浸润。PTEQ/siPD-L1+激光组不仅启动了 NIR-II 光热疗法,还促进了 T 细胞、M1 巨噬细胞极化和树突状细胞在 TME 中的激活和浸润,导致 7/10 例肿瘤完全消除,实现了 100%的存活率。在另一个体内疫苗实验中,PTEQ/siPD-L1+激光组右侧的所有肿瘤都完全消除,达到了 100%的肿瘤消除率。这些发现强调了这种策略克服当前免疫治疗限制并实现免疫治疗规范化的潜力。

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