Fabrication of macrophage-membrane coated functionalized ROS-responsive thiolated chitosan-based nanoparticles to attenuate atherosclerosis: Investigation on diabetic hyperlipidaemia-induced mice model.

BACKGROUND

Diabetic hyperlipidemia, which is characterized by oxidative stress and chronic inflammation, plays a significant role in atherosclerosis (AC), a key cause of cardiovascular disease. To reduce the progression of AC, effective treatment options that target the underlying causes of diabetic hyperlipidemia are required.

METHODOLOGY

This study used macrophage-membrane-loaded β-CD functionalized thiolated ROS-responsive NPs (MM@R-β-tCh NPs) as a targeted therapy for diabetic hyperlipidemia-induced AC. The NPs targeted MM and used the β-CD core's ROS sensitivity to deliver drugs to specific locations. Transmission electron microscopy (TEM) was employed to evaluate the structural characteristics. In vitro investigations with HUVEC and MOVAS cell lines evaluated the effect on inflammatory markers IL-6 and TNF-α. In vivo investigations utilizing an animal model evaluated the effects of nanoparticles on blood glucose, lipid concentrations, and arterial plaque levels.

RESULTS

The TEM analysis of MM@R-β-tCh NPs displayed the emergence of spherical nanoparticles with a diameter of 170 ± 8 nm. MM@R-β-tCh NPs exhibited high drug loading efficiency and ROS-triggered release, achieving 85 % release under enhanced ROS conditions. Accordingly, FRET index (1.8 ± 0.05) confirms the NP's ROS sensitivity. In vitro tests revealed substantial reductions in IL-6 and TNF-α levels. In vivo, findings decreased blood glucose (300 mg/dL to 90 mg/dL), total plasma cholesterol (37 % to 36 %), and serum triglycerides (40 %). H&E staining demonstrated that MM@R-β-tCh-NP-treated mice decreased macrophage infiltration and lipid accumulation in arterial plaques.

CONCLUSION

MM@R-β-tCh NPs successfully reduce oxidative stress and dyslipidemia, providing a targeted treatment approach for diabetic hyperlipidemia-induced AC. These findings suggest that MM@R-β-tCh NPs can reduce AC development and improve cardiovascular health in diabetics.