State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials, Ministry of Education, and College of Life Sciences, Nankai University, Tianjin, China.
Department of Urology, The First Affiliated Hospital of Soochow University, Suzhou, China.
Nat Commun. 2024 Nov 29;15(1):10395. doi: 10.1038/s41467-024-53906-x.
Activatable theranostic systems combining precise diagnosis and robust immune activation have significant potential in cancer treatment. Herein, we develop a versatile nanoplatform integrating hypoxia-activatable molecular imaging with effective photoimmunotherapy for cancer treatment. Our molecular probe features turn-on near-infrared-II (NIR-II) fluorescence and photoacoustic signals in hypoxic tumor environments. It also induces hypoxia-triggered photodynamic and photothermal effects, promoting immunogenic cell death and activating the STING pathway, engaging both innate and adaptive immunity. The molecular probe is formulated with a vascular disrupting agent to amplify the hypoxia-responsive phototheranostic properties, on which M1-like macrophage membrane is camouflaged to shield against premature release while conferring cancer-targeting affinity. The activatable NIR-II fluorescence and photoacoustic imaging enable precise tumor delineation, while the enhanced phototherapy activates tumor-specific cytotoxic T cells, impeding both primary and distant tumor progression and providing protective immunity against rechallenge in 4T1 tumor-bearing female mice. This work advances activatable theranostic protocols for image-guided immunotherapy.
可激活的治疗性系统将精确诊断和强大的免疫激活结合在一起，在癌症治疗方面具有巨大的潜力。在此，我们开发了一种多功能纳米平台，将缺氧激活的分子成像与有效的光免疫疗法结合起来用于癌症治疗。我们的分子探针在缺氧肿瘤环境中具有开启近红外二区（NIR-II）荧光和光声信号的特性。它还会引发缺氧触发的光动力和光热效应，促进免疫原性细胞死亡并激活 STING 途径，同时涉及先天免疫和适应性免疫。该分子探针用血管破坏剂进行了配方设计，以增强对缺氧的响应性光治疗特性，其上伪装了 M1 样巨噬细胞膜，以防止过早释放，并赋予对癌症的靶向亲和力。可激活的近红外二区荧光和光声成像能够精确描绘肿瘤，而增强的光疗则会激活肿瘤特异性细胞毒性 T 细胞，阻止原发性和远处肿瘤的进展，并为在 4T1 荷瘤雌性小鼠中进行再挑战提供保护免疫。这项工作推进了用于图像引导免疫治疗的可激活治疗性方案。
