Selenocystine-Derived Label-Free Fluorescent Schiff Base Nanocomplex for siRNA Delivery Synergistically Kills Cancer Cells

Molecules

Junfeng Ji¹  Yang Liu¹  Shiyuan Pan²  Jinfeng Wei²  Mingming Pan²  Haoying Yang²  Xiaowei Zhao²  Qian Liu²  Weiran Zhang²  Danli Wang³ 

[1] Center of Stem Cell and Regenerative Medicine, School of Medicine, Zhejiang University, Hangzhou 310058, China;Henan Key Laboratory of Brain Targeted Bio-Nanomedicine, School of Life Sciences & School of Pharmacy, Henan University, Kaifeng 475004, China;Zhoushan Hospital of Zhejiang Province, Zhoushan 316004, China;

关键词: selenocystine;    fluorescent Schiff base;    Schiff base probe;    siRNA nanoparticle;    tumor senescence;   

DOI  :  10.3390/molecules27041302

来源: DOAJ

【 摘 要 】

Chemo and siRNA synergic treatments for tumors is a promising new therapeutic trend. Selenocystine, a selenium analog of cysteine, has been considered a potential antitumor agent due to its redox perturbing role. In this study, we developed a nanocarrier for siRNA based on a selenocystine analog engineered polyetherimide and achieved traceable siRNA delivery and the synergic killing of tumor cells. Notably, we applied the label-free Schiff base fluorescence mechanism, which enabled us to trace the siRNA delivery and to monitor the selenocystine analogs’ local performance. A novel selenocystine-derived fluorescent Schiff base linker was used to crosslink the polyetherimide, thereby generating a traceable siRNA delivery vehicle with green fluorescence. Moreover, we found that this compound induced tumor cells to undergo senescence. Together with the delivery of a siRNA targeting the anti-apoptotic BCL-xl/w genes in senescent cells, it achieved a synergistic inhibition function by inducing both senescence and apoptosis of tumor cells. Therefore, this study provides insights into the development of label-free probes, prodrugs, and materials towards the synergic strategies for cancer therapy.

【 授权许可】

Unknown