Wang Yadong, Qiu Long, Ye Tianzhen, Tan Fuyuan, Lyu Jie, Li Feize, Sun Zhizhong, Yang Yuanyou, Zhang Jinsong, Liu Ning, Liao Jiali
Institute of Nuclear Science and Technology, Sichuan University, Chengdu, 610000, China.
Sichuan Engineering Research Center for Radioactive Isotope, National Engineering Research Center for Isotopes and Pharmaceuticals, Nuclear Power Institute of China, Chengdu, 610000, China.
Chembiochem. 2025 Feb 1;26(3):e202400579. doi: 10.1002/cbic.202400579. Epub 2025 Jan 2.
Radionuclide therapy is expected to be a powerful tool for glioma treatment. Here, we introduced a novel nuclear nanomedicine based on polydopamine (PDA), incorporating fibroblast activation protein inhibitor (FAPI) and macrocyclic chelator (DOTA) for specific cancer targeting and Lu labeling. The synthesized nanoradiopharmaceutical, Lu-DOTA-PEG-PDA-FAPI, exhibits good stability in serum, saline and PBS over 5 days. Lu-DOTA-PEG-PDA-FAPI shows efficient specific uptake and internalization when incubated with U87MG cells. In vivo distribution visualized prominent accumulation and long retention ability of Lu-DOTA-PEG-PDA-FAPI at tumor sites after local administration. Moreover, Lu-DOTA-PEG-PDA-FAPI has satisfactory antitumor ability without apparent toxic and side effects observed from therapy assay and H&E staining. This study highlights the feasibility of using PDA as a nanocarrier for glioma endoradiotherapy by targeting fibroblast activation protein.
放射性核素疗法有望成为治疗神经胶质瘤的有力工具。在此，我们介绍了一种基于聚多巴胺（PDA）的新型核纳米药物，其包含成纤维细胞活化蛋白抑制剂（FAPI）和大环螯合剂（DOTA），用于特异性癌症靶向和镥标记。合成的纳米放射性药物Lu-DOTA-PEG-PDA-FAPI在血清、生理盐水和PBS中5天内表现出良好的稳定性。与U87MG细胞孵育时，Lu-DOTA-PEG-PDA-FAPI显示出高效的特异性摄取和内化。体内分布显示，局部给药后，Lu-DOTA-PEG-PDA-FAPI在肿瘤部位有显著的蓄积和长期滞留能力。此外，Lu-DOTA-PEG-PDA-FAPI具有令人满意的抗肿瘤能力，治疗试验和苏木精-伊红染色未观察到明显的毒副作用。本研究强调了通过靶向成纤维细胞活化蛋白，使用PDA作为纳米载体进行神经胶质瘤内放射治疗的可行性。
