Inflammatory endothelium-targeted and cathepsin responsive nanoparticles are effective against atherosclerosis

Abstract

Rationale: Atherosclerosis is characterized by lipid accumulation, plaque formation, and artery stenosis. The pharmacological treatment is a promising therapy for atherosclerosis, but this approach faces major challenges such as targeted drug delivery, controlled release, and non-specific clearance. Methods: Based on the finding that the cathepsin k (CTSK) enzyme is enriched in atherosclerotic lesions, we constructed an integrin α v β 3 targeted and CTSK-responsive nanoparticle to control the release of rapamycin (RAP) locally. The targeted and responsive nanoparticles (T/R NPs) were engineered by the self-assembly of a targeting polymer PLGA-PEG-c(RGDfC) and a CTSK-sensitive polymer PLGA-Pep-PEG. PLGA-Pep-PEG was also modified with a pair of FRET probe to monitor the hydrolysis events. Results: Our results indicated that RAP@T/R NPs accelerated the release of RAP in response to CTSK stimulation in vitro , which significantly inhibited the phagocytosis of OxLDL and the release of cytokines by inflammatory macrophages. Additionally, T/R NPs had prolonged blood retention time and increased accumulation in the early and late stage of atherosclerosis lesions. RAP@T/R NPs significantly blocked the development of atherosclerosis and suppressed the systemic and local inflammation in ApoE -/- mice. Conclusions: RAP@T/R NPs hold a great promise as a drug delivery system for safer and more efficient therapy of atherosclerosis.

The Role of Thymoquinone in Inflammatory Response in Chronic Diseases

“…Atherosclerosis, a CVD, is mainly caused by endothelial injury accompanied by many inflammatory reactions. These reactions result in the oxidation of low-density lipoprotein (LDL) by macrophages to form peroxide and superoxide ions, SMC proliferation, and plaque formation in the vascular wall [ 81 ]. TQ was found to be involved in this process and is mainly effective in reducing the level of LDL to prevent foam cell formation through an antioxidant function.…”

Design and Fabrication of Environmentally Responsive Nanoparticles for the Diagnosis and Treatment of Atherosclerosis

“…This emerging field of research in drug delivery holds significant promise. In a study conducted by Fang et al, 88 NPs were engineered to target integrin αvβ3 and respond to the enzyme cathepsin K (CTSK) for controlled release of the drug RAP. It was discovered that CTSK is enriched in atherosclerotic lesions.…”

Advances in imaging and treatment of atherosclerosis based on organic nanoparticles

“…Currently, the most-studied polymeric NPs for anti-atherosclerosis are hyaluronic acid (HA)-based and PLGA-based NPs. 95–99 Recent studies have shown that HA NPs can actively target atherosclerotic plaques. 100 Hossaini Nasr et al assessed the anti-atherosclerosis effect of HA NPs loaded with the clinical drug atorvastatin and found that, compared to in the free atorvastatin group, the group with HA-NPs loaded with atorvastatin experienced a better anti-inflammatory effect in vivo and in vitro after 1 week of treatment.…”