Ultrasound-mediated delivery of Pik3cb shRNA using magnetic nanoparticles for the treatment of in-stent restenosis in a rat balloon-injured model

The aim of the present work was to examine the effect of polyethylene glycol (PEG)-coated superparamagnetic iron oxide (SPIO) nanoparticles carrying Pik3cb short hairpin RNA (shRNA) in the prevention of restenosis with the aid of ultrasound and a magnetic field. SPIO is a type of contrast agent used in medical imaging to enhance the visibility of specific tissues or organs. It consists of tiny iron oxide nanoparticles that can be targeted to specific areas of interest in the body. PEG-coated SPIO nanoparticles carrying Pik3cb shRNA (SPIO-shPik3cb) were prepared, and the particle size and zeta potential of PEG-coated SPIO nanoparticles with and without Pik3cb shRNA were examined. After a right common artery balloon-injured rat model was established, the rats were randomly divided into four groups, and the injured arteries were transfected with SPIO-shPik3cb, saline, SPIO-shcontrol and naked shRNA Pik3cb. During the treatment, each group was placed under a magnetic field and was transfected with the aid of ultrasound. Rats were sacrificed, and the tissue was harvested for analysis after 14 days. The results suggested that the mean particle size and zeta potential of SPIO-shPik3cbs were 151.45 ± 11 nm and 10 mV, respectively. SPIO-shPik3cb showed higher transfection efficiency and significantly inhibited the intimal thickening compared with naked Pik3cb shRNA in vascular smooth muscle cells (VSMCs) (^*P < 0.05). Moreover, SPIO-shPik3cb could also significantly downregulate the expression of pAkt protein compared with naked Pik3cb shRNA. According to the results, SPIO-shPik3cb can remarkably inhibit the intimal thickening under a combination of magnetic field exposure and ultrasound. (author)