Visualizing miR-155 To Monitor Breast Tumorigenesis and Response to Chemotherapeutic Drugs by a Self-Assembled Photoacoustic Nanoprobe

Abstract

MicroRNA-155 (miR-155), which facilitates breast tumor growth and invasion by promoting tumor cell proliferation and inhibiting cell apoptosis, is considered an ideal early diagnostic and prognostic marker. Herein, we developed a self-assembled hybridization chain reaction (HCR)-based photoacoustic (PA) nanoprobe for highly sensitive in situ monitoring of dynamic changes in miR-155 expression during breast tumorigenesis and chemotherapy. The PA nanoprobes (Au-H1/PEG and Au-H2/PEG) were constructed by linking poly(ethylene glycol) (PEG) and two hairpin DNA strands (H1 and H2, respectively) to the surface of gold nanoparticles (AuNPs). In the presence of miR-155, the PA nanoprobes self-assembled into Au aggregates via HCR between H1, H2, and miR-155. The decreased interparticle distance in these aggregates enhanced the surface plasmon resonance (SPR) in the AuNPs. Consequently, the absorption peak of the PA nanoprobes red-shifted, and strong PA signals were generated. This strategy enabled the sensitive and quantitative detection of miR-155 with a low detection limit of 0.25 nM. As a result, PA signals of miR-155 were captured on the second day after tumor inoculation when the solid tumor had not yet formed. Dynamic changes in miR-155 during tumor growth and chemotherapy were also monitored in real time to assess the therapeutic effects via PA imaging. By virtue of these advantages, the PA nanoprobes may provide a powerful platform for in situ detection of miR-155 and thus real-time monitoring of tumorigenesis and drug response in breast cancer.