Dual-microRNA triggered and DNA-programmed nanomachine for subtype-based detection and tailored treatment of breast cancer cells

Abstract

Discriminative detection and precise therapy targeting specific subtypes of breast cancers are critical for improving the treatment efficacy and thereby improving the survival rates of patients. Herein, we developed a dual-microRNA triggered DNA-programmed nanomachine for effective discrimination and modulated chemotherapy based on the subtypes of breast cancer cells. Two microRNA stimuli (miR-21 and miR-10b) can trigger the conformation change of the DNA nanomachine assembled on gold nanoparticles (AuNPs) through the toehold-mediated strand displacement reactions (TSDR), during which the fluorescence resonance energy transfer (FRET) signal is generated for microRNA imaging and the loaded doxorubicin (DOX) molecules are released for chemotherapy. The nanomachine can detect miR-10b as low as 0.047 nmol/L (S/N = 3) at a fixed concentration of miR-21 with high selectivity. Moreover, it allows effective discrimination of highly metastatic MDA-MB-231 breast cancer cells from non-metastatic MCF-7 breast cancer cells based on the dual microRNA expression patterns, and adjusts the DOX dosage according to the metastatic activity of cancer. This intelligent nanomachine with controlled release of anti-cancer drug in specific cancer cell subtypes can reduce the side effect to normal cells and facilitate the targeted therapy, which is promising as a theranostics nanoplatform in precise medicine.