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Prodrug-based combinational nanomedicine remodels lipid metabolism for reinforced ferroptosis and immune activation

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Pubmed体系：

收录情况： ◇ 统计源期刊 ◇ CSCD-C ◇ 卓越：领军期刊

作者：
Lin Ling[1] * ; Fang Zaixiang[1] * ; Liu Guohao[1] ; Liu Yiwei[1] ; Li Zhiqian[1] ; Pan Dayi[1] ; Li Yunkun[1] ; Kang Hemi[2] ; Shen Xiaoding[1] ; Zhang Jingyao[1] ; Gong Qiyong[1,3,4] ; Luo Kui[1,3] ; Jing Jing[1] ;
机构： [1]Department of Radiology, Huaxi MR Research Center (HMRRC), Institution of Radiology and Medical Imaging, Breast Center, Institute of Breast Health Medicine, State Key Laboratory of Biotherapy, Core Facilities, West China Hospital, Sichuan University, Chengdu 610041, China. [2]College of Chemical Engineering, Sichuan University, Chengdu 610041, China. [3]Functional and Molecular Imaging Key Laboratory of Sichuan Province, NHC Key Laboratory of Transplant Engineering and Immunology, Research Unit of Psychoradiology, Chinese Academy of Medical Sciences, Chengdu 610041, China. [4]Xiamen Key Lab of Psychoradiology and Neuromodulation, Department of Radiology, West China Xiamen Hospital of Sichuan University, Xiamen 361021, China.
出处：
DOI： 10.1016/j.apsb.2025.03.016
ISSN：

关键词： Prodrug-based nanomedicines Ferroptosis Lipid metabolism Immune activation Breast cancer Heparin Combinational therapy ROS-responsiveness

摘要：
Ferroptosis is a form of programmed cell death characterized by overwhelmed lipid oxidation, and it has emerged as a promising strategy for cancer therapy. Enhanced ferroptosis could overcome the limitations of conventional therapeutic modalities, particularly in difficult-to-treat tumors. In this study, we developed a dual-modality therapy in nanomedicine by combining paclitaxel (PTX) chemotherapy and pyropheophorbide-a (Ppa) phototherapy. Heparin (HP) was grafted with poly(N-(2'-hydroxy) propyl methacrylamide) (pHPMA) using reversible addition-fragmentation chain transfer polymerization to form HP-pHPMA (HH), which was utilized to deliver Ppa and PTX, yielding HP-pHPMA-Ppa (HH-Ppa) and HP-pHPMA-PTX (HH-PTX), respectively. The prodrug-based combinational nanomedicine (HH-PP) was formed by co-assembly of HH-PTX and HH-Ppa. It was found that HH-PP treatment significantly disrupted lipid metabolism in triple-negative breast cancer (TNBC) cells, induced extensive lipid oxidation, and promoted ferroptosis. In vivo, HH-PP intervention achieved a tumor growth inhibition rate of 86.63% and activated adaptive immunity with an elevated CD8+ cytotoxic T cell infiltration level. This combinational nanomedicine offers a promising platform for co-delivery of multiple therapeutic agents. It exerts a promising anti-tumor effect via enhanced ferroptosis and ferroptosis-induced immune activation by disrupting lipid metabolism in TNBC cancer cells.© 2025 The Authors.

基金：
This work was financially supported by the National Key Research and Development Program of China (2023ZD0502304, 2023YFB3810004, 2022YFC2009900), Natural Science Foundation of China (32271445, 52073193), Department of Science and Technology of Sichuan Province (2024NSFJQ0050, China),National Guidance Fund on Developing Local Science and Technology for Sichuan Province (2023ZYD0167, China), 1‧3‧5 project for disciplines of excellence, West China Hospital, Sichuan University (ZYGD23026, China).
语种：
外文
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中科院(CAS)分区：
出版当年[2025]版：
大类 | 1 区 医学
小类 | 1 区 药学
最新[2025]版：
大类 | 1 区 医学
小类 | 1 区 药学
第一作者：
第一作者机构： [1]Department of Radiology, Huaxi MR Research Center (HMRRC), Institution of Radiology and Medical Imaging, Breast Center, Institute of Breast Health Medicine, State Key Laboratory of Biotherapy, Core Facilities, West China Hospital, Sichuan University, Chengdu 610041, China.
共同第一作者：
通讯作者：
通讯机构： [1]Department of Radiology, Huaxi MR Research Center (HMRRC), Institution of Radiology and Medical Imaging, Breast Center, Institute of Breast Health Medicine, State Key Laboratory of Biotherapy, Core Facilities, West China Hospital, Sichuan University, Chengdu 610041, China. [3]Functional and Molecular Imaging Key Laboratory of Sichuan Province, NHC Key Laboratory of Transplant Engineering and Immunology, Research Unit of Psychoradiology, Chinese Academy of Medical Sciences, Chengdu 610041, China. [4]Xiamen Key Lab of Psychoradiology and Neuromodulation, Department of Radiology, West China Xiamen Hospital of Sichuan University, Xiamen 361021, China.
推荐引用方式(GB/T 7714)：
Lin Ling,Fang Zaixiang,Liu Guohao,et al.Prodrug-based combinational nanomedicine remodels lipid metabolism for reinforced ferroptosis and immune activation[J].Acta Pharmaceutica Sinica B.2025,15(5):2746-2763.doi:10.1016/j.apsb.2025.03.016.
APA：
Lin Ling,Fang Zaixiang,Liu Guohao,Liu Yiwei,Li Zhiqian...&Jing Jing.(2025).Prodrug-based combinational nanomedicine remodels lipid metabolism for reinforced ferroptosis and immune activation.Acta Pharmaceutica Sinica B,15,(5)
MLA：
Lin Ling,et al."Prodrug-based combinational nanomedicine remodels lipid metabolism for reinforced ferroptosis and immune activation".Acta Pharmaceutica Sinica B 15..5(2025):2746-2763

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