Reactive Oxygen Species Activatable Heterodimeric Prodrug as Tumor-Selective Nanotheranostics

前药 活性氧 喜树碱 化学 光动力疗法 细胞毒性 光敏剂 癌细胞 连接器 药品 生物物理学 生物化学 癌症研究 药理学 癌症 体外 有机化学 生物 操作系统 遗传学 计算机科学
作者
Meijuan Jiang,Jing Mu,Orit Jacobson,Zhantong Wang,Liangcan He,Fuwu Zhang,Weijing Yang,Qiaoya Lin,Zijian Zhou,Ying Ma,Jing Lin,Junle Qu,Peng Huang,Xiaohong Chen
出处
期刊:ACS Nano [American Chemical Society]
卷期号:14 (12): 16875-16886 被引量:57
标识
DOI:10.1021/acsnano.0c05722
摘要

Nanotheranostics based on tumor-selective small molecular prodrugs could be more advantageous in clinical translation for cancer treatment, given its defined chemical structure, high drug loading efficiency, controlled drug release, and reduced side effects. To this end, we have designed and synthesized a reactive oxygen species (ROS)-activatable heterodimeric prodrug, namely, HRC, and nanoformulated it for tumor-selective imaging and synergistic chemo- and photodynamic therapy. The prodrug consists of the chemodrug camptothecin (CPT), the photosensitizer 2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-a (HPPH), and a thioketal linker. Compared to CPT- or HPPH-loaded polymeric nanoparticles (NPs), HRC-loaded NPs possess higher drug loading capacity, better colloidal stability, and less premature drug leakage. Interestingly, HRC NPs were almost nonfluorescent due to the strong π-π stacking and could be effectively activated by endogenous ROS once entering cells. Thanks to the higher ROS levels in cancer cells than normal cells, HRC NPs could selectively light up the cancer cells and exhibit much more potent cytotoxicity to cancer cells. Moreover, HRC NPs demonstrated highly effective tumor accumulation and synergistic tumor inhibition with reduced side effects on mice.
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