A microRNA-21-responsive doxorubicin-releasing sticky-flare for synergistic anticancer with silencing of microRNA and chemotherapy

• 作者: Min Hong Hongxiao Sun Qiangqiang Yang Shuang Cheng Shuxian Yu Shuhua Fan Chuan Li Cheng Cui Weihong Tan
• 来源期刊: 中国科学：化学（英文版）
• 年，卷（期）: 2021,（6）
• 所属期刊栏目: ARTICLES
• 页码范围: 1009-1019
• 页数: 11页
• 语种: 英文

摘要

A sticky-flare gold nanoparticle probe (AuNP-probe) is designed by the combination of locked nucleic acid functionalized silencing of microRNA technology for intracellular microRNA-21 (miRNA-21) sensitively detecting,fluorescence imaging,localizing and silencing.The limit of detection is as low as 0.01 nM.Overexpressed miRNA-21 in cancer cells serves as endogenous drug release stimuli to trigger the release of probe-loaded doxorubicin (Dox),which soon translocates into cell nuclei.This multifunctional Dox-loaded AuNP-probe (Dox-AuNP-probe) could induce cancer cell apoptosis effectively through the synergistic effect of gene silencing and chemotherapy.This Dox-AuNP-probe exhibits superior drug potency compared to free Dox molecules,with a cell inhibition rate of 57％ (but only 20％ for Dox) to wild-type cancer cells and 30％ (but 0％ for Dox) to drug-resistent cancer cells after 72 h,and this strategy not only has the function of sensing,but also can effectively bypass drug resistance.In MCF-7 xenograft tumor-bearing mice,the Dox-AuNP-probes show greater inhibition for tumor tissues than miRNA-21 targeted AuNP-probes (Targeting-AuNP-probe) or free Dox molecules.Therefore,the Dox-AuNP-probe represents a promising nanotheranostic platform for future applications in cancer molecular imaging and therapy,especially providing a potential strategy to treat resistant cancers.