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

Abstract

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.