2. Academic Validation
  3. Multifunctional Nanomedicine for Targeted Atherosclerosis Therapy: Activating Plaque Clearance Cascade and Suppressing Inflammation

Multifunctional Nanomedicine for Targeted Atherosclerosis Therapy: Activating Plaque Clearance Cascade and Suppressing Inflammation

  • ACS Nano. 2025 Jan 28;19(3):3339-3361. doi: 10.1021/acsnano.4c12131.
Cui Tang 1 2 3,  Hui Wang 3,  Lina Guo 1,  Yimin Cui 4,  Chan Zou 3,  Jianming Hu 5,  Hanyong Zhang 6,  Guoping Yang 1 3 7 8,  Wenhu Zhou 1 6 9
Affiliations

Affiliations

  • 1 Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, Hunan 410013, China.
  • 2 Department of Pharmacy, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
  • 3 Center of Clinical Pharmacology, the Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, China.
  • 4 Department of Pharmacy, Peking University First Hospital, Beijing 100034, China.
  • 5 First Department of Pathology, Affiliated Hospital, Shihezi University, Xinjiang Uygur Autonomous Region, Shihezi City 832002, China.
  • 6 Academician Workstation, Changsha Medical University, Changsha 410219, China.
  • 7 National-Local Joint Engineering Laboratory of Drug Clinical Evaluation Technology, Changsha, Hunan 410000, China.
  • 8 Hunan Engineering Research Center for Optimization of Drug Formulation and Early Clinical Evaluation, Changsha, Hunan 410013, China.
  • 9 NHC Key Laboratory of Prevention and Treatment of Central Asia High Incidence Diseases, Affiliated Hospital, Shihezi University, Shihezi City, Xinjiang 832002, China.
PMID: 39812806 DOI: 10.1021/acsnano.4c12131
Abstract

Atherosclerosis (AS) is a prevalent inflammatory vascular disease characterized by plaque formation, primarily composed of foam cells laden with lipids. Despite lipid-lowering therapies, effective plaque clearance remains challenging due to the overexpression of the CD47 molecule on apoptotic foam cells, inhibiting macrophage-mediated cellular efferocytosis and plaque resolution. Moreover, AS lesions are often associated with severe inflammation and oxidative stress, exacerbating disease progression. Herein, we introduce a multifunctional nanomedicine (CEZP) targeting AS pathogenesis via a "cell efferocytosis-lipid degradation-cholesterol efflux" paradigm, with additional anti-inflammatory properties. CEZP comprises poly(lactic-co-glycolic acid) nanoparticles encapsulated within a metal-organic framework shell coordinated with zinc ions (Zn2+) and epigallocatechin gallate (EGCG), enabling CpG encapsulation. Upon intravenous administration, CEZP accumulates at AS plaque sites, facilitating macrophage uptake and orchestrating AS treatment through synergistic mechanisms. CpG enhances cellular efferocytosis, Zn2+ promotes intracellular lipid degradation, and EGCG upregulates adenosine 5'-triphosphate-binding cassette transporters for Cholesterol efflux while also exhibiting antioxidant and anti-inflammatory effects. In vivo validation confirms CEZP's ability to stabilize plaques, reduce lipid burden, and modulate the macrophage phenotype. Moreover, CEZP is excreted from the body without safety concerns, offering a low-toxicity nonsurgical strategy for AS plaque eradication.

Keywords

ROS scavenging; autophagy; cholesterol efflux; efferocytosis; macrophage polarization; metal−organic frameworks.

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