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A Targeted and Responsive Nanoprodrug Delivery System for Synergistic Glioma Chemotherapy

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机构： [1]Department of Neurosurgery and Institute of Neurosurgery, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, China. [2]Department of Laboratory Medicine, West China Second University Hospital, Sichuan University, Chengdu, 610041, China. [3]Key Laboratory of Birth Defects and Related Diseases of Women and Children(Sichuan University), Ministry of Education, Chengdu, 610041, China. [4]West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, 610041, China.

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关键词： BBB penetration curcumin DOX prodrug glioma GSH-responsive tumor microenvironment

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Doxorubicin (DOX) is widely used as a chemotherapeutic agent for both hematologic and solid tumors and is a reasonable candidate for glioma treatment. However, its effectiveness is hindered by significant toxicity and drug resistance. Moreover, the presence of the blood-brain barrier (BBB) brings a crucial challenge to glioma therapy. In response, a GSH-responsive and actively targeted nanoprodrug delivery system (cRGD/PSDOX-Cur@NPs) are developed. In this system, a disulfide bond-bridged DOX prodrug (PEG-SS-DOX) is designed to release specifically in the high glutathione (GSH) tumor environment, markedly reducing the cardiotoxicity associated with DOX. To further address DOX resistance, curcumin, serving as a P-glycoprotein (P-gp) inhibitor, effectively increased cellular DOX concentration. Consequently, cRGD/PSDOX-Cur@NPs exhibited synergistic anti-tumor effects in vitro. Furthermore, in vivo experiments validated the superior BBB penetration and brain-targeting abilities of cRGD/PSDOX-Cur@NPs, showcasing the remarkable potential for treating both subcutaneous and orthotopic gliomas. This research underscores that this nanoprodrug delivery system presents a novel approach to inhibiting glioma while addressing resistance and systemic toxicity.© 2024 Wiley-VCH GmbH.

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大类 | 2 区

材料科学

小类 | 1 区物理：应用 2 区化学：综合 2 区物理化学 2 区材料科学：综合 2 区纳米科技 2 区物理：凝聚态物理

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第一作者机构： [1]Department of Neurosurgery and Institute of Neurosurgery, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, China.

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