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Disruption of Ferroptosis Inhibition and Immune Evasion with Tumor-Activatable Prodrug for Boosted Photodynamic/Chemotherapy Eradication of Drug-Resistant Tumors

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机构： [1]National Traditional Chinese Medicine Clinical Research Base and Drug Research Center of Integrated Traditional Chinese and Western Medicine, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, Sichuan, 646000, China. [2]Institute of Integrated Chinese and Western Medicine, Southwest Medical University, Luzhou, Sichuan, 646000, China. [3]State Key Laboratories for Quality Research in Chinese Medicines, Faculty of Chinese Medicine, Macau University of Science and Technology, Macau, 999078, China. [4]Experimental Medicine Center, The Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan, 646000, China.

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关键词： doxorubicin drug resistant ferroptosis glutathione immune evasion mitochondria photodynamic puerarin TSPO protein

摘要：

Breast cancer is a malignant tumor that threatens the life and health of women worldwide. As the first-line chemotherapy drug for breast cancer, doxorubicin (DOX) can inhibit the synthesis of RNA and DNA, and it exhibits strong inhibitory activity against breast cancer. However, drug-induced systemic toxicity and drug resistance can occur with DOX treatment. In this work, TSPO protein is identified as a promising target for overcoming drug resistance and we designed a novel BT-DOX/PDP conjugate to solve these problems in drug chemotherapy. It is found that BT-DOX/PDP can effectively downregulate TSPO1 protein and sensitize MCF-7/Adr to DOX. Furthermore, due to its positive charge, BT-DOX/PDP is readily loaded into puerarin (PUE), the resulting BT-DOX/PDP@PUE exhibited minimal systemic toxicity but enhanced antitumor activity in animal models, as compared with BT-DOX/PDP. This study demonstrates the advantages of combined chemotherapy and photodynamic therapy in overcoming drug resistance, which may be applied in the design of other photodynamic therapy-based conjugates to enhance antitumor therapy.© 2024 Wiley‐VCH GmbH.

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大类 | 2 区

医学

小类 | 2 区工程：生物医学 2 区材料科学：生物材料 2 区纳米科技

第一作者：

第一作者机构： [1]National Traditional Chinese Medicine Clinical Research Base and Drug Research Center of Integrated Traditional Chinese and Western Medicine, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, Sichuan, 646000, China. [2]Institute of Integrated Chinese and Western Medicine, Southwest Medical University, Luzhou, Sichuan, 646000, China. [3]State Key Laboratories for Quality Research in Chinese Medicines, Faculty of Chinese Medicine, Macau University of Science and Technology, Macau, 999078, China.

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通讯作者：

通讯机构： [1]National Traditional Chinese Medicine Clinical Research Base and Drug Research Center of Integrated Traditional Chinese and Western Medicine, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, Sichuan, 646000, China. [2]Institute of Integrated Chinese and Western Medicine, Southwest Medical University, Luzhou, Sichuan, 646000, China.

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Disruption of Ferroptosis Inhibition and Immune Evasion with Tumor-Activatable Prodrug for Boosted Photodynamic/Chemotherapy Eradication of Drug-Resistant Tumors

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