Pretargeted radiotherapy and synergistic treatment of metastatic, castration-resistant prostate cancer using cross-linked, PSMA-targeted lipoic acid nanoparticles
机构：[1]Department of Nuclear Medicine and Huaxi MR Research Center (HMRRC), Functional and Molecular Imaging Key Laboratory of Sichuan Province and Frontiers Science Center for Disease Related Molecular Network, West China Hospital, Sichuan University, China四川大学华西医院[2]Department of Nuclear Medicine, West China Hospital, Sichuan University, 37 Guoxue Alley, Chengdu 610041, Sichuan, China四川大学华西医院[3]College of Biomedical Engineering and National Engineering Research Center for Biomaterials, Sichuan University, 29 Wangjiang Road, Chengdu 610064, China.[4]Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, China四川大学华西医院[5]of Nuclear Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China重庆医科大学附属第一医院
Metastatic castration-resistant prostate cancer (CRPC) is a currently incurable disease associated with high mortality. Novel therapeutic approaches for CRPC are urgently needed to improve prognosis. In this study, we developed cross-linked, PSMA-targeted lipoic acid nanoparticles (cPLANPs), which can interact with transmembrane glycoprotein to accumulate inside prostate cancer cells, where they upregulate caspase-3, downregulate anti-apoptotic B-cell lymphoma-2 (BCL-2), and thereby induce apoptosis. The trans-cyclooctene (TCO) decoration on cPLANPs acts as a bioorthogonal handle allowing pretargeted single-photon emission computed tomography and radiotherapy, which revealed significantly enhanced tumor accumulation and minimal off-target toxicity in our experiments. The developed strategy showed a strong synergistic anti-cancer effect in vivo, with a tumor inhibition rate of up to 95.6% after 14 days of treatment. Our results suggest the potential of combining bioorthogonal pretargeted radiotherapy with suitable PSMA-targeted nanoparticles for the treatment of metastatic CRPC. A potent strategy based on cross-linked, PSMA-targeted lipoic acid nanoparticles revealed the great potential of pretargeted radiotherapy for the synergistic treatment of metastatic castration-resistant prostate cancer.
基金：
National Natural Science Foundation of China [21975165, 81901776, 81971653, 21907070]; Project for disciplines of excellence at West China Hospital, Sichuan University [ZYYC23003]; Sichuan Science and Technology Innovation Foundation [2021JDTD0015]
第一作者机构：[1]Department of Nuclear Medicine and Huaxi MR Research Center (HMRRC), Functional and Molecular Imaging Key Laboratory of Sichuan Province and Frontiers Science Center for Disease Related Molecular Network, West China Hospital, Sichuan University, China
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通讯作者：
推荐引用方式(GB/T 7714)：
Dai Liqun,Zhang Xiaoyang,Zhou Siming,et al.Pretargeted radiotherapy and synergistic treatment of metastatic, castration-resistant prostate cancer using cross-linked, PSMA-targeted lipoic acid nanoparticles[J].JOURNAL OF MATERIALS CHEMISTRY B.2024,12(9):2324-2333.doi:10.1039/d3tb02543h.
APA：
Dai, Liqun,Zhang, Xiaoyang,Zhou, Siming,Li, Jie,Pan, Lili...&Wu, Haoxing.(2024).Pretargeted radiotherapy and synergistic treatment of metastatic, castration-resistant prostate cancer using cross-linked, PSMA-targeted lipoic acid nanoparticles.JOURNAL OF MATERIALS CHEMISTRY B,12,(9)
MLA：
Dai, Liqun,et al."Pretargeted radiotherapy and synergistic treatment of metastatic, castration-resistant prostate cancer using cross-linked, PSMA-targeted lipoic acid nanoparticles".JOURNAL OF MATERIALS CHEMISTRY B 12..9(2024):2324-2333
