Redox-responsive drug delivery nanoparticles with integrated capabilities of ROS scavenging, lipid removal and anti-inflammation

Atherosclerosis, a leading cause of cardiovascular morbidity and mortality, is characterized by elevated reactive oxygen species (ROS), lipid accumulation, and chronic inflammation in plaques. Targeted drug delivery using nanotechnology represents a promising therapeutic strategy aligned with these pathological features. Herein, a multifunctional nanotherapeutic system was reported, engineered to integrate ROS-responsive drug release, lipid-removing capability, and anti-inflammatory functions. The nanoparticle comprised a ROS-sensitive disulfide bond bridging lipid-sequestering cyclodextrin and natural anti-inflammatory epigallocatechin gallate (EGCG), loaded with the atherogenic drug pitavastatin calcium (Pi). Leveraging the enhanced permeability and retention (EPR) effect, the nanoparticles preferentially accumulated at atherosclerotic lesions. The nanotherapeutic system exhibited excellent biosafety, ROS-scavenging ability, and intelligent drug release proportional to environmental oxidative levels. Furthermore, the system promoted endothelial cell proliferation, suppresses smooth muscle cell hyperplasia, and reduces pro-inflammatory cytokine secretion. Combined with its capacity to clear lipids, this multifunctional nano-therapy exhibited promising potential for atherosclerosis treatment.