2. Academic Validation
  3. Pitavastatin and resveratrol bio-nanocomplexes against hyperhomocysteinemia-induced atherosclerosis via blocking ferroptosis-related lipid deposition

Pitavastatin and resveratrol bio-nanocomplexes against hyperhomocysteinemia-induced atherosclerosis via blocking ferroptosis-related lipid deposition

  • J Control Release. 2025 Mar 3:381:113598. doi: 10.1016/j.jconrel.2025.113598.
Anning Yang 1,  Hongwen Zhang 2,  Huiping Zhang 3,  Nan Li 2,  Cong Chen 4,  Xiaoling Yang 2,  Jue Tian 2,  Jianmin Sun 2,  Guizhong Li 2,  Yue Sun 5,  Bin Liu 6,  Yideng Jiang 7
Affiliations

Affiliations

  • 1 General Hospital, School of Basic Medical Sciences, Ningxia Medical University, Yinchuan 750004, China; NHC Key Laboratory of Metabolic Cardiovascular Diseases Research, Ningxia Medical University, Yinchuan 750004, China; College of Biology, Hunan University, Changsha 410082, China; Ningxia Key Laboratory of Vascular Injury and Repair Research, Yinchuan 750004, China.
  • 2 General Hospital, School of Basic Medical Sciences, Ningxia Medical University, Yinchuan 750004, China; NHC Key Laboratory of Metabolic Cardiovascular Diseases Research, Ningxia Medical University, Yinchuan 750004, China; Ningxia Key Laboratory of Vascular Injury and Repair Research, Yinchuan 750004, China.
  • 3 General Hospital, School of Basic Medical Sciences, Ningxia Medical University, Yinchuan 750004, China; NHC Key Laboratory of Metabolic Cardiovascular Diseases Research, Ningxia Medical University, Yinchuan 750004, China; Hunan Provincial Maternal and Child Health Care Hospital, Changsha 410000, China.
  • 4 Hunan University of Chinese Medicine, Changsha 410208, China.
  • 5 General Hospital, School of Basic Medical Sciences, Ningxia Medical University, Yinchuan 750004, China; NHC Key Laboratory of Metabolic Cardiovascular Diseases Research, Ningxia Medical University, Yinchuan 750004, China; School of Public Health and Management, Ningxia Medical University, Yinchuan 750004, China; Ningxia Key Laboratory of Vascular Injury and Repair Research, Yinchuan 750004, China. Electronic address: sunyue@nxmu.edu.cn.
  • 6 General Hospital, School of Basic Medical Sciences, Ningxia Medical University, Yinchuan 750004, China; NHC Key Laboratory of Metabolic Cardiovascular Diseases Research, Ningxia Medical University, Yinchuan 750004, China; College of Biology, Hunan University, Changsha 410082, China. Electronic address: binliu2001@hotmail.com.
  • 7 General Hospital, School of Basic Medical Sciences, Ningxia Medical University, Yinchuan 750004, China; NHC Key Laboratory of Metabolic Cardiovascular Diseases Research, Ningxia Medical University, Yinchuan 750004, China; Ningxia Key Laboratory of Vascular Injury and Repair Research, Yinchuan 750004, China. Electronic address: jydeng@nxmu.edu.cn.
PMID: 40043912 DOI: 10.1016/j.jconrel.2025.113598
Abstract

Atherosclerosis (AS) therapy has been commonly based on lipid-lowering agents (e.g., statins), supplemented by Other therapies, such as anti-inflammatory agents and Antioxidants, through traditional Chinese herbs. Ferroptosis, a form of regulated cell death characterized by iron-dependent lipid peroxidation, has been implicated in the progression of AS, particularly in macrophages. In the study, we constructed a macrophage targeted hybridization nanodrug of HMLRPP, which used Pit-loaded Poly(lactic-co-glycolic) acid (PLGA) nanoparticles (NPs) and Res-loaded liposomes as nano-core, then, coated with a macrophage membrane hybridized by hyaluronic acid. The nanodrug prolonged blood circulation time and achieved optimal Res and Pit accumulation in the atherosclerotic plaques by effectively evading immune system clearance. In vivo studies demonstrated that HMLRPP NPs significantly attenuated plaque progression, characterized by decreased plaque area, less lipid deposition, and increased collagen. Meanwhile, HMLRPP NPs inhibited macrophage Ferroptosis by decreasing the expression of β-Hydroxybutyrate dehydrogenase 1 (BDH1), Orosomucoid 1 (ORM1) and enhancing the expression of Ribosomal protein S27-like (RPS27L), which resulted in the alleviation of lipid accumulation and inflammation. Our data suggest that the HMLRPP nanodrug delivery system with ferroptosis-regulating capability provides a feasible therapeutic strategy for atherosclerosis.

Keywords

Atherosclerosis; Homocysteine; Nano-delivery; Pitavastatin; Resveratrol.

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