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,fluo...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 n M.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.展开更多
基金This work was supported by the Natural Science Foundation of Shandong Province(ZR2015BM024)“Shandong Province Tai-Shan Program”,China Scholarship Council(CSC)scholarship to Dr.Hong,and the National Natural Science Foundation of China(21729501).
文摘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 n M.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.
