2. Academic Validation
  3. Targeted gene delivery of shear-responsive forkhead box C1 using hyaluronic acid modified chitosan nanoparticles suppresses atherosclerosis through Hippo-YAP signaling pathway

Targeted gene delivery of shear-responsive forkhead box C1 using hyaluronic acid modified chitosan nanoparticles suppresses atherosclerosis through Hippo-YAP signaling pathway

  • Int J Biol Macromol. 2025 Oct 14;330(Pt 4):148307. doi: 10.1016/j.ijbiomac.2025.148307.
Rui Hai 1,  Wenzhuo Liu 2,  Fei Wu 3,  Sawitree Chiampanichayakul 4,  Singkome Tima 4,  Chunhong Li 5,  Songyot Anuchapreeda 6,  Xiangyu Zhou 7
Affiliations

Affiliations

  • 1 Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, 50200, Thailand; Department of Breast, Thyroid, Vascular Surgery, the Affiliated Hospital of Traditional Chinese Medicine of Southwest Medical University, Luzhou, 646000, China.
  • 2 Department of Thyroid and Breast Surgery, Chengdu Integrated TCM&Western Medicine Hospital, Chengdu, 610000, China; Southwest Medical University, Luzhou, 646000, China.
  • 3 Department of General Surgery (Thyroid Surgery), the Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China.
  • 4 Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, 50200, Thailand; Cancer Research Unit of Associated Medical Sciences (AMS CRU), Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, 50200, Thailand; Center of Excellence in Pharmaceutical Nanotechnology, Faculty of Pharmacy, Chiang Mai University, Chiang Mai, 50200, Thailand.
  • 5 Department of Pharmaceutical Sciences, School of Pharmacy, Southwest Medical University, Luzhou, 646000, China. Electronic address: lispringhong@126.com.
  • 6 Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, 50200, Thailand; Cancer Research Unit of Associated Medical Sciences (AMS CRU), Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, 50200, Thailand; Center of Excellence in Pharmaceutical Nanotechnology, Faculty of Pharmacy, Chiang Mai University, Chiang Mai, 50200, Thailand. Electronic address: songyot.anuch@cmu.ac.th.
  • 7 Department of General Surgery (Thyroid Surgery), the Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China. Electronic address: xiangyuzhou971@vip.126.com.
PMID: 41101410 DOI: 10.1016/j.ijbiomac.2025.148307
Abstract

Previous studies have demonstrated that shear force stress from blood flow plays a crucial role in the onset and progression of atherosclerosis (AS), primarily by modulating endothelial cell function, inflammation, and oxidative stress. In this study, we identified Forkhead box C1 (FOXC1) as a shear-response transcription factor whose expression is significantly upregulated by unidirectional laminar flow (UF). Knockdown of FOXC1 in human umbilical vein endothelial cells (HUVECs) partially alleviated inflammation and Autophagy dysregulation via modulation of the Hippo-YAP signaling pathway, suggesting that FOXC1 may serve as a potential therapeutic target for AS. To enhance targeted FOXC1 expression, we developed chitosan nanoparticles encapsulating FOXC1 plasmids, further modified with hyaluronic acid (HA) to achieve active target via CD44 receptors expressed on endothelial cells. These HA-modified nanoparticles exhibited excellent biological stability and targeting efficiency, leading to a significant reduction in atherosclerotic plaque formation in vivo. Our findings suggest that this nanoparticle-based FOXC1 delivery system holds great promise as a novel therapeutic strategy for the treatment of AS.

Keywords

Atherosclerosis; FOXC1; Nanoparticles.

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