Dual-responsive Targeted Atherosclerosis Therapy through a Multi-effective Nanoplatform with Anti-inflammatory, Lipid-regulating and Autophagy

The traditional treatment of atherosclerosis (AS) is mainly focused on lipid-lowering therapy, through oral statins to reduce blood lipid levels and control the progress of AS. However, current oral drug therapy has suffered from poor targeting and single efficacy. Here, a pH-responsive magnetic nanoplatforms (MMNS@AT-CS-DS) was developed. The dextran sulfate (DS) was encapsulated on MMNS@AT-CS to endow the nanoplatforms with the property of targeting atherosclerotic plaques. In vitro and in vivo results showed that MMNS@AT-CS-DS could target lesion areas and release statins to slow the progression of AS due to the magnetocaloric effect under alternating magnetic field (AMF) and dissolution of chitosan (CS) in the AS induced low pH environment. More importantly, its magneto-thermal responsiveness could induce protective autophagy to treat AS synergistically. In addition, the magnetic nanoplatforms could perform magnetic resonance (MR) imaging of atherosclerotic plaques, which shed new light on the integration of diagnosis and treatment of AS.