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  3. High-throughput screening-based design of multifunctional natural polyphenol nano-vesicles to accelerate diabetic wound healing

High-throughput screening-based design of multifunctional natural polyphenol nano-vesicles to accelerate diabetic wound healing

  • J Nanobiotechnology. 2024 Nov 21;22(1):725. doi: 10.1186/s12951-024-02950-2.
Xiaoying Zhao # 1 2 3,  Shenkai Su # 1 2 3,  Chenyu Wu 1 2 3,  Yuxin Deng 1 2 3,  Yu Chen 1 2 3,  Tanxin Yu 1 2 3,  Chenchao Li 1 2 3,  Yekai Zhang # 1 2 3,  Xiangyang Wang 4 5 6,  Yifei Zhou 7 8 9,  Xiaolei Zhang 10 11 12
Affiliations

Affiliations

  • 1 Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China.
  • 2 Zhejiang Provincial Key Laboratory of Orthopedics, Wenzhou, Zhejiang Province, China.
  • 3 The Second School of Medicine, Wenzhou Medical University, Wenzhou, Zhejiang Province, China.
  • 4 Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China. xiangyangwang@wmu.edu.cn.
  • 5 Zhejiang Provincial Key Laboratory of Orthopedics, Wenzhou, Zhejiang Province, China. xiangyangwang@wmu.edu.cn.
  • 6 The Second School of Medicine, Wenzhou Medical University, Wenzhou, Zhejiang Province, China. xiangyangwang@wmu.edu.cn.
  • 7 Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China. yifeizhou@wmu.edu.cn.
  • 8 Zhejiang Provincial Key Laboratory of Orthopedics, Wenzhou, Zhejiang Province, China. yifeizhou@wmu.edu.cn.
  • 9 The Second School of Medicine, Wenzhou Medical University, Wenzhou, Zhejiang Province, China. yifeizhou@wmu.edu.cn.
  • 10 Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China. zhangxiaolei@wmu.edu.cn.
  • 11 Zhejiang Provincial Key Laboratory of Orthopedics, Wenzhou, Zhejiang Province, China. zhangxiaolei@wmu.edu.cn.
  • 12 The Second School of Medicine, Wenzhou Medical University, Wenzhou, Zhejiang Province, China. zhangxiaolei@wmu.edu.cn.
  • # Contributed equally.
PMID: 39574119 DOI: 10.1186/s12951-024-02950-2
Abstract

Oxidative stress is a major pathological factor that impedes the diabetic wound healing process. Procyanidins (PC) form nanoparticle-vesicles (PPNs) through hydrogen bonding and exhibit good drug delivery capability; however, their application in diabetic wounds is unsatisfactory. To meet the antioxidant needs for treating, high-throughput screening in the natural product library (NPL) under in vitro oxidative stress conditions was conducted to enhance the antioxidant activity of PPNs. HUVECs treated with tert-Butyl Hydroperoxide (TBHP) were established as screening model in vitro. Baicalein (BAI) was identified from over 600 products in the library as the most effective one to combat oxidative stress. Further study showed that PC and BAI may react in equal proportions to synthesize new vesicles, named BAI-PC Polyphenolic nanovesicles (BPPNs), which possess Reactive Oxygen Species (ROS) responsive and antioxidant effects. Network pharmacology indicated that in diabetic wounds, the target genes of PC are mainly enriched in the vascular endothelial growth factor (VEGF)-related pathways, while BAI primarily regulates tyrosine phosphorylation. The complementarity between the two has been validated in both in vitro and in vivo experiments. In summary, the antioxidant drug BAI, identified through high-throughput screening of NPL, could optimize the biological function of PPNs; the newly-synthesized BPPNs may accelerate diabetic wound healing through dual mechanisms of promoting angiogenesis and combating oxidative stress.

Keywords

Antioxidative stress; Diabetic wound healing; Natural product library; Peptidyl-tyrosine phosphorylation; Polyphenol nanovesicles.

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