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Blockade of metastasis by targeting circulating tumor cells with platelet encapsuled oncolytic adenovirus

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机构： [1]Institute of Breast Health Medicine, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, Chengdu, Sichuan, 610041, PR China [2]Institute of Breast Health Medicine, Ultrasound Department, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, PR China [3]Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, PR China [4]Department of Immunology, School of Basic Medical Sciences, Chengdu Medical College, Chengdu, Sichuan, 610500, PR China [5]College of Chemical Engineering, Shijiazhuang University, Shijiazhuang, Hebei, 050035, PR China [6]Animal Experimental Center, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, PR China [7]Breast Center, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, PR China [8]Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, West China School of Pharmacy, Sichuan University, Chengdu, Sichuan, 610064, PR China

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关键词： Circulating tumor cell Platelet Oncolytic adenovirus Tumor metastasis Biotherapy

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Host immune elimination largely limits the application of oncolytic viruses in clinics. Here, we rationally design a bioactive platelet-based oncolytic adenovirus delivery system. Upon loading adenoviruses, platelets are transformed to a pro-endocytosis status, which facilitates their internalization by circulating tumor cells (CTCs). The CTCs are enriched into metastatic organs by tumor homing effect. The internalized adenoviruses de-coat cover and initiate their oncolytic life cycle, leading to a vigorous immunogenic cell death (ICD) in the metastatic niche. In both a spontaneous metastasis model and a tail vein injection-based CTC dissemination model, intravenous administration of adenovirus-loaded platelets significantly inhibits lung metastasis. Remarkably, this regimen successfully evokes the host immune system in the metastatic organ by inducing tumor ICD. In conclusion, our bioactive delivery system not only largely resolves the bottleneck problem of oncolytic virus application but also provides a foundation for joint immune therapy in clinics.Copyright © 2025. Published by Elsevier Ltd.

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出版当年[2025]版：

大类 | 1 区

医学

小类 | 1 区工程：生物医学 1 区材料科学：生物材料

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大类 | 1 区

医学

小类 | 1 区工程：生物医学 1 区材料科学：生物材料

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第一作者机构： [1]Institute of Breast Health Medicine, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, Chengdu, Sichuan, 610041, PR China [3]Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, PR China

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