Lipophilic NO‐Driven Nanomotors as Drug Balloon Coating for the Treatment of Atherosclerosis

Abstract Drug‐coated balloons (DCB) intervention is an important approach for the treatment of atherosclerosis (AS). However, this therapeutic approach has the drawbacks of poor drug retention and penetration at the lesion site. Here, a lipophilic drug‐loaded nanomotor as a modified balloon coating for the treatment of AS is reported. First, a lipophilic nanomotor PMA‐TPP/PTX loaded with drug PTX and lipophilic triphenylphosphine (TPP) compounds is synthesized. The PMA‐TPP/PTX nanomotors use nitric oxide (NO) as the driving force, which is produced from the reaction between arginine on the motor substrate and excess reactive oxygen species (ROS) and inducible nitric oxide synthase (iNOS) in the AS microenvironment. The final in vitro and in vivo experimental results confirm that the introduction of the lipophilic drug‐loaded nanomotor technology can greatly enhance the drug retention and permeability in atherosclerotic lesions. In particular, NO can also play an anti‐AS role in improving endothelial cell function and reducing oxidative stress. The chemotherapeutic drug PTX loaded onto the nanomotors can inhibit cell division and proliferation, thereby exerting the effect of inhibiting vascular intimal hyperplasia, which is helpful for the multiple therapies of AS. Using nanomotor technology to solve cardiovascular diseases may be a promising research direction.