Abstract
MicroRNAs (miRNAs) are emerging as vital biomarkers since their abnormal expression is associated with various disease types including cancer. Therefore, it is essential to develop a sensitive and specific platform to monitor the dynamic expression of miRNAs for early clinical diagnosis and treatment. In this study, we designed a functionalized polydopamine (PDA)-based theranostic nanoprobe for efficient detection of miRNA-21 and in vivo synergistic cancer therapy. PDA was modified with polyethylene glycol (PEG) and the obtained PDA-PEG nanoparticles showed good stability in different solutions. PDA-PEG nanoparticles were loaded with fluorescein isothiocyanate (FITC)-labeled hairpin DNA (hpDNA) and an anticancer drug doxorubicin (DOX). In the absence of miRNA-21, PDA effectively quenched the fluorescence of FITC-labeled hpDNA. The presence of miRNA-21 specifically recognized hpDNA and induced the dissociation of hpDNA from PDA-PEG and subsequently recovered the fluorescence signals. Upon cellular uptake of these nanoprobes, a dose-dependent fluorescence activation and synergetic cytotoxic effect were observed due to the release of DOX and inhibition of miRNA-21 function. Furthermore, PDA-PEG-DOX-hpDNA nanoparticles can afford long-term monitoring of miRNA-21 and combined therapeutic efficacy in the nude mice bearing 4T1 tumors. Our results demonstrate the capability of PDA-PEG-DOX-hpDNA as a theranostic nanoprobe for continuously tracking of miRNAs and synergetic cancer therapy.