2. Academic Validation
  3. Coptis chinensis extracellular vesicles loaded with CA1-siRNA promote endothelial repair and stent restenosis therapy by regulating the PADI2 and NF-κB pathway

Coptis chinensis extracellular vesicles loaded with CA1-siRNA promote endothelial repair and stent restenosis therapy by regulating the PADI2 and NF-κB pathway

  • J Nanobiotechnology. 2026 Feb 11;24(1):157. doi: 10.1186/s12951-026-04092-z.
Xinxing Wang # 1,  Yan Liu # 2,  Wei Li # 1,  Juan Hao 3,  Zhongjie Zhao 1,  Hua Fan 1,  Xiumin Wu 4,  Xiangyu Liu 1,  Haowen Xu 1,  Tao Yu 5,  Mingyuan Liu 6,  Mingjin Guo 7,  Yongxin Li 8
Affiliations

Affiliations

  • 1 Department of Vascular Surgery, The Affiliated Hospital of Qingdao University, No.1677 Wutaishan Road, Qingdao, 266000, Shandong, People's Republic of China.
  • 2 Center for Regenerative Medicine, Institute for Translational Medicine, The Affiliated Hospital of Qingdao University, No.38 Deng Zhou Road, Qingdao, 266021, Shandong, People's Republic of China.
  • 3 Department of Gynecology, Women and Children's Hospital, Qingdao University, Qingdao, 266000, People's Republic of China.
  • 4 Department of Medical Imaging, The Affiliated Hospital of Qingdao University, Qingdao, 266000, Shandong, People's Republic of China.
  • 5 Center for Regenerative Medicine, Institute for Translational Medicine, The Affiliated Hospital of Qingdao University, No.38 Deng Zhou Road, Qingdao, 266021, Shandong, People's Republic of China. [email protected].
  • 6 Department of Vascular Surgery, Beijing Friendship Hospital, Capital Medical University, No.95 Yongan Road, Xicheng district, Beijing, 100000, People's Republic of China. [email protected].
  • 7 Department of Vascular Surgery, The Affiliated Hospital of Qingdao University, No.1677 Wutaishan Road, Qingdao, 266000, Shandong, People's Republic of China. [email protected].
  • 8 Department of Vascular Surgery, The Affiliated Hospital of Qingdao University, No.1677 Wutaishan Road, Qingdao, 266000, Shandong, People's Republic of China. [email protected].
  • # Contributed equally.
PMID: 41673867 DOI: 10.1186/s12951-026-04092-z
Abstract

In-stent restenosis (ISR), a chronic vascular proliferative disorder, poses significant clinical challenges due to impaired endothelial repair, suboptimal long-term outcomes of interventional therapies, and complications associated with current preventive strategies. Although gene therapy offers a promising approach for ISR management, its clinical translation is hindered by the scarcity of innovative gene-based drugs and the lack of efficient delivery systems. Here, we identify Carbonic Anhydrase 1 (CA1) as a potential target in regulating endothelial cell survival, regeneration, and inflammatory responses. We then engineered plant-derived exosome-like nanoparticles (CLENs) to encapsulate CA1-siRNA, enabling targeted delivery and enhanced stability. CLENs (siRNA) exhibit prolonged circulation and precise accumulation at aortic lesions, effectively reducing ISR rates. Mechanistically, this therapeutic approach alleviates endothelial inflammatory activation by suppressing the NF-κB and TNF signaling pathways and downregulating PADI2 expression, while also demonstrating favorable biosafety. Our study presents a novel plant-derived nano-delivery system based on purely natural components for early ISR intervention, which demonstrates both therapeutic efficacy and an absence of adverse effects.

Keywords

Carbonic anhydrase 1; Endothelial cell; In-stent restenosis; Inflammation; Plant-derived nanomaterials.

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