A nanoprobe for fluorescent monitoring of microRNA and targeted delivery of drugs

Abstract

Multifunctional nano-materials that can be used to monitor the expression of specific biomarkers and serve as vehicles for controlled drug delivery are highly desirable. Herein, we report a new DNA-hybrid-gated core–shell upconversion nanoprobe (UCNP@MOF/DOX) for fluorescence analysis of microRNA-21 (miR-21), which also triggers the release of drug loaded in the probes for on-demand anti-cancer treatment. The nanoprobe is built on the merits of ultraviolet-visible light of upconversion nanoparticles (UCNPs) excited by near-infrared (NIR) and extraordinary loading capability of metal–organic frameworks (MOFs) for drug delivery. Controlled release of doxorubicin (DOX) from the nanoprobe by miR-21 underwent the following two-stage kinetics: a fast release stage specifically triggered by miR-21 and proportional to miR-21 concentration and a slow stage observed in both gated and ungated nanoprobes due to collapse of the UIO-66-NH₂ coatings via ligand exchange with phosphates. In addition, the nanoprobe showed good selectivity, a linear response towards miR-21 ranging from 4 nM to 500 nM, and a limit of detection in 4 nM, which precluded unintended payload leakage due to low-abundance endogenous miR-21 expression in normal cells. Moreover, based on a dual-targeted delivery system constituted by AS1411-mediated recognition and responsive release of DOX, a specific cytotoxic efficacy was observed in MCF-7 cells. The present work provides a smart and robust nanoprobe for real-time detection of miRNA and dual-responsive drug delivery in tumor cells.