MicroRNA-Catalyzed Cancer Therapeutics Based on DNA-Programmed Nanoparticle Complex

The use of cancer-relevant microRNA molecules as endogenous drug release stimuli is promising for personalized cancer treatment yet remains a great challenge because of their low abundance. Herein, we report a new type of microRNA-catalyzed drug release system based on DNA-programmed gold nanoparticle (GNP)–quantum dot (QD) complex. We show that a trace amount of miRNA-21 molecules could specifically catalyze the disassembly of doxorubicin (Dox)-loaded GNP–QDs complex through entropy driven process, during which the Dox-intercalating sites are destructed for drug release. This catalytic reaction could proceed both in fixed cells and live cells with miRNA-21 overexpression. Dox molecules could be efficiently released in the cells and translocate to cell nuclei. QD photoluminescence is simultaneously activated during catalytic disassembly process, thus providing a reliable feedback for microRNA-triggered drug release. The GNP–QDs–Dox complex exhibits much higher drug potency than free Dox molecules, and therefore represents a promising platform for accurate and effective cancer cell treatment.