Ultrasound monitoring of magnet-guided delivery of mesenchymal stem cells labeled with magnetic lipid-polymer hybrid nanobubbles.

Restenosis remains a pressing clinical problem that occurs in patients undergoing revascularization procedures, such as coronary artery bypass surgery and percutaneous transluminal angioplasty. Previous reports have proved that mesenchymal stem cells (MSCs) could effectively reduce the restenosis resulting from intimal hyperplasia following vascular injury. However, non-invasive delivery of MSCs and real-time monitoring of their retention at the site of vascular injury still remain a significant challenge. Therefore, we synthesized magnetic lipid–polymer hybrid nanobubbles (Mag-LPNs) as ultrasound contrast agents for cellular labeling of MSCs, endowing these MSCs with magnetic responsibility and real-time tracking capability by ultrasound. In order to enhance the internalization efficiency of MSCs, Mag-LPNs were modified with cationic polymers to generate positively charged Mag-LPNs (P-Mag-LPNs). Intriguingly, the internalization of P-Mag-LPNs did not exhibit obvious harmful effects on the labeled MSCs in terms of cell viability and differentiation capacity. Moreover, the magnet-guided delivery of labeled MSCs in a rat carotid artery injury model developed using a 2-French balloon catheter could be tracked by ultrasound in a real-time manner. About 5-fold more MSCs were attached at the site of the injured artery with the aid of an external magnet field, compared with the absence of a magnet field. Herein, our study provides an innovative tracking platform for magnet-guided delivery of stem cells treating cardiovascular diseases.