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Co-delivery of SN38 and SR717 activates cGAS-STING for near-infrared II image-guided chemoimmunotherapy

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机构： [1]Department of Radiology, Zhongnan Hospital of Wuhan University, School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, China [2]State Key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China [3]Shandong Laboratory of Yantai Drug Discovery, Bohai Rim Advanced Research Institute for Drug Discovery, Yantai 264117, China [4]Shenzhen Institute of Wuhan University, Shenzhen 518057, China [5]Medical College of Tibet University, Lasa 850002, China [6]Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China

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关键词： cGAS-STING activation Immunotherapy NIR-II fluorescence imaging Long-circulating

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DNA-targeting chemotherapies can activate the stimulator of interferon genes (STING) pathway but elicit limited immune responses. We engineered 3P-SN38, a long-circulating nanoplatform enabling sustained, tumor-targeted SN38 delivery and NIR-II imaging. To further potentiate immune activation and minimize STING agonist toxicity, SR717 was co-encapsulated, forming 3P-SN38@SR717. 3P-SN38@SR717 induced immunogenic cell death and dendritic cell maturation in vitro, with combination therapy showing superior effects. In vivo, 3P-SN38@SR717 effectively activated the cGAS-STING pathway, enhancing anti-tumor immunity. Significant increases in the populations of CD8+ T cells, mature dendritic cells, and M1-type macrophages were observed, along with elevated levels of cytokines, including IL-6 and TNF-α. This integrated nanoplatform offers a promising approach for chemoimmunotherapy, enabling durable tumor control with reduced dosing and improved safety.Copyright © 2025 Elsevier B.V. All rights reserved.

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出版当年[2025]版：

大类 | 1 区

医学

小类 | 1 区药学 2 区化学：综合

最新[2025]版：

大类 | 1 区

医学

小类 | 1 区药学 2 区化学：综合

第一作者：

第一作者机构： [1]Department of Radiology, Zhongnan Hospital of Wuhan University, School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, China [2]State Key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China [3]Shandong Laboratory of Yantai Drug Discovery, Bohai Rim Advanced Research Institute for Drug Discovery, Yantai 264117, China

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通讯机构： [2]State Key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China [3]Shandong Laboratory of Yantai Drug Discovery, Bohai Rim Advanced Research Institute for Drug Discovery, Yantai 264117, China [4]Shenzhen Institute of Wuhan University, Shenzhen 518057, China

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Co-delivery of SN38 and SR717 activates cGAS-STING for near-infrared II image-guided chemoimmunotherapy

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