"Pretargeted radiotherapy and synergistic treatment of metastatic, castration-resistant prostate cancer using cross-linked, PSMA-targeted lipoic acid nanoparticles"

作者全名："Dai, Liqun; Zhang, Xiaoyang; Zhou, Siming; Li, Jie; Pan, Lili; Liao, Chunyan; Wang, Zhipeng; Chen, Ying; Shen, Guohua; Li, Lin; Tian, Rong; Sun, Hongbao; Liu, Zhenhua; Zhang, Shiyong; Wu, Haoxing"

作者地址："[Dai, Liqun; Zhou, Siming; Li, Jie; Sun, Hongbao; Wu, Haoxing] Sichuan Univ, West China Hosp, Dept Nucl Med, Chengdu, Peoples R China; [Dai, Liqun; Zhou, Siming; Li, Jie; Sun, Hongbao; Wu, Haoxing] Sichuan Univ, West China Hosp, Huaxi MR Res Ctr HMRRC, Funct & Mol Imaging Key Lab Sichuan Prov, Chengdu, Peoples R China; [Dai, Liqun; Zhou, Siming; Li, Jie; Sun, Hongbao; Wu, Haoxing] Sichuan Univ, West China Hosp, Frontiers Sci Ctr Dis Related Mol Network, Chengdu, Peoples R China; [Zhang, Xiaoyang; Pan, Lili; Shen, Guohua; Li, Lin; Tian, Rong] Sichuan Univ, West China Hosp, Dept Nucl Med, 37 Guoxue Alley, Chengdu 610041, Sichuan, Peoples R China; [Liao, Chunyan; Chen, Ying; Zhang, Shiyong] Sichuan Univ, Coll Biomed Engn, 29 Wangjiang Rd, Chengdu 610064, Peoples R China; [Liao, Chunyan; Chen, Ying; Zhang, Shiyong] Sichuan Univ, Natl Engn Res Ctr Biomat, 29 Wangjiang Rd, Chengdu 610064, Peoples R China; [Wang, Zhipeng; Liu, Zhenhua] Sichuan Univ, West China Hosp, Inst Urol, Dept Urol, Chengdu, Peoples R China; [Zhang, Xiaoyang] Chongqing Med Univ, Affiliated Hosp 1, Dept Nucl Med, Chongqing 400016, Peoples R China"

通信作者："Wu, HX (通讯作者)，Sichuan Univ, West China Hosp, Dept Nucl Med, Chengdu, Peoples R China.; Wu, HX (通讯作者)，Sichuan Univ, West China Hosp, Huaxi MR Res Ctr HMRRC, Funct & Mol Imaging Key Lab Sichuan Prov, Chengdu, Peoples R China.; Wu, HX (通讯作者)，Sichuan Univ, West China Hosp, Frontiers Sci Ctr Dis Related Mol Network, Chengdu, Peoples R China.; Zhang, SY (通讯作者)，Sichuan Univ, Coll Biomed Engn, 29 Wangjiang Rd, Chengdu 610064, Peoples R China.; Zhang, SY (通讯作者)，Sichuan Univ, Natl Engn Res Ctr Biomat, 29 Wangjiang Rd, Chengdu 610064, Peoples R China.; Liu, ZH (通讯作者)，Sichuan Univ, West China Hosp, Inst Urol, Dept Urol, Chengdu, Peoples R China."

来源：JOURNAL OF MATERIALS CHEMISTRY B

ESI学科分类：MATERIALS SCIENCE

WOS号：WOS:001157808900001

JCR分区：Q2

影响因子：7

年份：2024

卷号：　

期号：　

开始页：　

结束页：　

文献类型：Article; Early Access

关键词：　

摘要："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."

基金机构："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]"

基金资助正文："This work was supported by the National Natural Science Foundation of China (21975165, 81901776, 81971653, and 21907070), the 1.3.5 project for disciplines of excellence at West China Hospital, Sichuan University (ZYYC23003), and Sichuan Science and Technology Innovation Foundation (2021JDTD0015)."