前药
醛脱氢酶
癌症研究
癌症
纳米-
化学
细胞
分子生物学
生物化学
医学
酶
内科学
材料科学
生物
复合材料
作者
Bin Liu,Bowen Li,Jianwu Tian,Fu Zhang,Chongzhi Wu,Zhiyao Li,Dandan Wang,Jiahao Zhuang,Siqin Chen,Wentao Song,Yufu Tang,Ping Yuan
出处
期刊:Research Square - Research Square
日期:2024-05-09
标识
DOI:10.21203/rs.3.rs-4319425/v1
摘要
Abstract Cancer stem cells (CSCs), characterized by high tumorigenicity and drug-resistance, are often responsible for tumor progression and metastasis. Aldehyde dehydrogenases (ALDH), often overexpressed in CSC-enriched tumors, present a potential target for specific anti-CSC treatment. In this study, we report a self-assembled nano-prodrug (PS-CHO@ATRA-SS-ATRA) composed of ALDH-activatable photosensitizer (PS-CHO) and disulfide-linked all-trans retinoic acid (ATRA-SS-ATRA) for diagnose and targeted treatment of CSC-enriched tumors. The ATRA-SS-ATRA can load with PS-CHO and self-assemble into a stable nanoparticle PS-CHO@ATRA-SS-ATRA, which can be disassembled into ATRA and PS-CHO in CSC by high level of GSH. As for released PS-CHO, overexpressed ALDH catalyzes the oxidation of aldehydes (-CHO) to carboxyl (-COOH) under CSC-enriched microenvironment, activating the generation of reactive oxygen species (ROS) and fluorescence emission. This ROS generation leads to direct killing of CSCs and is accompanied by a noticeable fluorescence enhancement for real-time monitoring of the CSC-enriched microenvironment. Moreover, the released ATRA, as a differentiation agent, reduce the CSCs stemness and improve the CSC-enriched microenvironment, offering a synergistic effect for enhanced anti-CSC treatment of PS-CHO in inhibition of in vivo tumor growth and metastasis.
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