KPV and RAPA Self‐Assembled into Carrier‐Free Nanodrugs for Vascular Calcification Therapy

Abstract Cardiovascular disease (CVD) is a leading cause of death globally, and vascular calcification (VC) is an important independent risk factor for predicting CVD. Currently, there are no established therapeutic strategies for the treatment of VC. Although recognized combination therapies of nanomedicines can provide effective strategies for disease treatment, the clinical application of nanomedicines is limited because of their complex preparation processes, low drug loading rates, and unpredictable safety risks. Thus, developing a simple, efficient, and safe nanodrug to simultaneously regulate inflammation and autophagy may be a promising strategy for treating VC. Herein, an anti‐inflammatory peptide (lysine‐proline‐valine peptides, KPV) and the autophagy activator rapamycin (RAPA) are self‐assembled to form new carrier‐free spherical nanoparticles (NPs), which shows good stability and biosafety. In vivo and in vitro, KPV‐RAPA NPs significantly inhibit VC in mice compared to the other treatment groups. Mechanistically, KPV‐RAPA NPs inhibit inflammatory responses and activated autophagy. Therefore, this study indicates that the new carrier‐free KPV‐RAPA NPs have great potential as therapeutic agents for VC combination therapy, which can promote the development of nanodrugs for VC.