Fibroblast activation protein α activatable theranostic pro-photosensitizer for accurate tumor imaging and highly-specific photodynamic therapy.
Fibroblast activation protein α activatable theranostic pro-photosensitizer for accurate tumor imaging and highly-specific photodynamic therapy.
复制标题
成纤维细胞活化蛋白α可激活的治疗诊断前光敏剂，用于精确的肿瘤成像和高度特异性的光动力治疗。
DOI：
10.7150/thno.70308
复制
发表时间：
2022
期刊：
影响因子：
12.4
通讯作者：
Zhao, Chunshun
中科院分区：
文献类型：
--
作者：
Luo, Yong;Zeng, Zishan;Shan, Ting;Xu, Xiaoyu;Chen, Jie;He, Yuanfeng;Zhang, Tao;Huang, Zeqian;Chai, Guihong;Huang, Yanjuan;Zhao, Yanfang;Zhao, Chunshun
关键词：
The development of activatable photosensitizers (aPSs) responding to tumor-specific biomarkers for precision photodynamic therapy (PDT) is urgently required. Due to the unique proteolytic activity and highly restricted distribution of tumor-specific enzymes, enzyme activatable photosensitizers display superior selectivity. Methods: Herein, a series of novel Fibroblast Activation Protein α (FAPα) activatable theranostic pro-photosensitizers were designed by conjugating the different N-terminal blocked FAPα-sensitive dipeptide substrates with a clinical PS, methylene blue (MB), through a self-immolative linker, which resulting in the annihilation of the photoactivity (fluorescence and phototoxicity). The best FAPα-responsive pro-photosensitizer was screened out through hydrolytic efficiency and blood stability. Subsequently, a series of in vitro and in vivo experiments were carried out to investigate the FAPα responsiveness and enhanced PDT efficacy. Results: The pro-photosensitizers could be effectively activated by tumor-specific FAPα in the tumor sites. After response to FAPα, the “uncaged” MB can recover its fluorescence and phototoxicity for tumor imaging and cytotoxic singlet oxygen (1O2) generation, eventually achieving accurate imaging-guided PDT. Simultaneously, the generated azaquinone methide (AQM) could serve as a glutathione (GSH) scavenger to rapidly and irreversibly weaken intracellular antioxidant capacity, realizing synergistic oxidative stress amplification and enhanced PDT effect. Conclusion: This novel FAPα activatable theranostic pro-photosensitizers allow for accurate tumor imaging and admirable PDT efficacy with minimal systemic side effects, offering great potential in clinical precision antitumor application.
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