ROS-Responsive Cinnamaldehyde Polymer Nanoparticles Loaded with Puerarin for the Treatment of Atherosclerosis.

Puerarin (PU) helps slow down and control the harmful progression of atherosclerosis (AS) by reducing inflammation, inhibiting foam cell formation, and exhibiting anticoagulant effects. However, its clinical application is limited due to its low bioavailability and other drawbacks. In recent years, nanoparticle-based therapeutic strategies targeting reactive oxygen species (ROS) at AS pathological sites and enhancing drug bioavailability and biocompatibility have shown great potential for AS treatment. In this study, we developed ROS-responsive cinnamaldehyde polymer nanoparticles loaded with PU (RGCP@PU NPs) for the treatment of AS. These nanoparticles demonstrate good stability and biocompatibility in physiological environments and can respond to ROS in the AS pathological environment, thereby releasing the encapsulated PU. In vitro experiments showed that these nanoparticles effectively inhibited oxidative stress and inflammation levels. In in vivo studies, RGCP@PU NPs were able to stabilize atherosclerotic plaques, prevent their further deterioration, and delay the progression of AS. Moreover, compared to free PU, these nanoparticles exhibited superior therapeutic effects in inhibiting AS progression. Therefore, RGCP@PU NPs represent a promising nanocarrier that not only effectively suppresses AS progression but also provides a new approach for the design of responsive drug delivery systems for AS treatment.