Ultrasound-Aided Targeting Nanoparticles Loaded with miR-181b for Anti-Inflammatory Treatment of TNF-α-Stimulated Endothelial Cells

[Image: see text] Gene therapy is an emerging therapeutic strategy used in clinics. Ultrasound-mediated gene transfection possesses great potential as a secure and available approach for gene delivery. However, transfection efficiency and targeting ability remain challenging. In this study, we developed a kind of ultrasound-aided and targeting nanoparticles for microRNA delivery. These nanoparticles carrying nucleic acids were prepared with cationic poly-(amino acid) encapsulated with perfluoropentane. The formulated nanoparticles were stabilized with negatively charged PGA–PEG–RGD peptide coating. Ultrasound imaging and specific gene transfection using this nanocarrier could be implemented simultaneously. Upon treatment with ultrasound irradiation, phase transition was induced in the nanoparticles and they generated acoustic cavitation, resulting in enhanced gene transfection against the endothelial cells. With the overexpression of miR-181b loaded by the nanoparticles, the TNF-α-stimulated endothelial cells were effectively rescued from the inflammatory state through the protection of cell viability and suppression of cell adhesion.