2. Academic Validation
  3. Inflammation-targeted nanoparticles modulate macrophage polarization for coronary therapy in Kawasaki disease

Inflammation-targeted nanoparticles modulate macrophage polarization for coronary therapy in Kawasaki disease

  • J Control Release. 2025 Oct 22;388(Pt 2):114350. doi: 10.1016/j.jconrel.2025.114350.
Zhiwei Chen 1,  Xinyu Di 2,  Heyan Chen 1,  Shengnan Song 2,  Siyi Zhu 1,  Leer Cai 1,  Yuqi Han 2,  Yongshuai Kang 1,  Dingchao Shen 1,  Huirong Huang 2,  Aimin Cai 1,  Hailun Zheng 1,  Qing Yao 2,  Maoping Chu 3,  Ruijie Chen 4,  Longfa Kou 5
Affiliations

Affiliations

  • 1 Wenzhou Municipal Key Laboratory of Pediatric Pharmacy, Department of Pharmacy, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China.
  • 2 Wenzhou Municipal Key Laboratory of Pediatric Pharmacy, Department of Pharmacy, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China; School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, China.
  • 3 Key Laboratory of Structural Malformations in Children of Zhejiang Province, Wenzhou 325027, China. Electronic address: chmping@hotmail.com.
  • 4 Wenzhou Municipal Key Laboratory of Pediatric Pharmacy, Department of Pharmacy, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China; Key Laboratory of Structural Malformations in Children of Zhejiang Province, Wenzhou 325027, China. Electronic address: crjpharm@163.com.
  • 5 Wenzhou Municipal Key Laboratory of Pediatric Pharmacy, Department of Pharmacy, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China; Key Laboratory of Structural Malformations in Children of Zhejiang Province, Wenzhou 325027, China. Electronic address: klfpharm@163.com.
PMID: 41135700 DOI: 10.1016/j.jconrel.2025.114350
Abstract

Coronary artery lesions are a major complication of Kawasaki disease (KD), where the local microenvironment is marked by excessive oxidative stress and persistent inflammation, presenting significant challenges for effective treatment. M1-polarized macrophages dominate these lesions, releasing pro-inflammatory mediators that aggravate vascular injury. Regulating macrophage polarization from the M1 to M2 phenotype thus offers a promising therapeutic strategy. Here, we developed a Reactive Oxygen Species (ROS)-responsive nanoplatform, HA-Sim@BRPL, to deliver simvastatin (Sim) specifically to inflamed coronary tissues. The nanocarrier is constructed from poly-l-lysine conjugated with bilirubin (BR), which self-assembles and enables ROS-triggered Sim release through BR's oxidative conversion to hydrophilic biliverdin. Surface decoration with hyaluronic acid (HA) facilitates selective uptake by CD44-expressing macrophages rather than cardiomyocytes. HA-Sim@BRPL effectively reduces intracellular ROS, promotes M2 macrophage polarization, and enhances endothelial cell survival via intercellular signaling. In a KD mouse model, HA-Sim@BRPL significantly attenuated coronary artery lesions and improved cardiac function. These results highlight a rationally designed nanomedicine that integrates oxidative stress responsiveness and inflammatory cell targeting, providing a promising therapeutic approach for coronary complications in KD.

Keywords

Coronary lesions; Kawasaki disease; Macrophage polarization; Nanoplatform; Simvastatin.

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