Multifunctional Plasmonic Core-Satellites Nanoprobe for Cancer Diagnosis and Therapy Based on a Cascade Reaction Induced by MicroRNA.

Constructing multifunctional plasmonic core-satellites (CS) nanoassembly for clinical cancer diagnosis and therapy has gained vast attention. Herein, we reported a doxorubicin (Dox)-loaded CS nanoprobe for microRNA (miRNA) detection, targeting drug release, and therapy evaluation. The plasmonic CS nanoprobe was constructed with uniformly distributional 50 nm (core) and 13 nm (satellites) gold nanoparticles (AuNPs), which were functionally assembled with a specific sequence of DNA and peptides. Anticancer drug Dox was loaded by intercalating into the GC-rich double strands. In the presence of target miRNA (miRNA-21 used as model), the constructed CS nanostructure was disassembled, producing characteristic localized surface plasmon resonance (LSPR) signals and releasing Dox. With the increase of the miRNA-21 concentration ranging from 0.01 to 1000 fM, a distinct blue shift of scattering spectra peak occurred, along with obvious color change from orange to green under a dark-field microscope (DFM), which can be used to detect miRNA at single-particle level. Meanwhile, it released Dox-induced apoptosis. Caspase-3 involved in apoptosis was then activated to cleave the specific peptide substrate, releasing fluorophore FAM from AuNPs. As a result, caspase-3 was detected based on restored fluorescence intensity, which was used to evaluate the therapy effectiveness. In a word, the multifunctional plasmonic CS nanoprobe can be used not only to image cellular miRNA-21 to distinguish tumor cells from normal cells, but also to release drugs and monitor the apoptotic process in situ by confocal imaging.