2. Academic Validation
  3. Promoting collateral formation in type 2 diabetes mellitus using ultra-small nanodots with autophagy activation and ROS scavenging

Promoting collateral formation in type 2 diabetes mellitus using ultra-small nanodots with autophagy activation and ROS scavenging

  • J Nanobiotechnology. 2024 Mar 1;22(1):85. doi: 10.1186/s12951-024-02357-z.
Yixuan Wang # 1 2,  Feifei Li # 1 2,  Linshuang Mao 1 2,  Yu Liu 3,  Shuai Chen 1 2,  Jingmeng Liu 1 2,  Ke Huang 1 2,  Qiujing Chen 1 2,  Jianrong Wu 4,  Lin Lu 1 2,  Yuanyi Zheng 4,  Weifeng Shen 1 2,  Tao Ying 5,  Yang Dai 6 7,  Ying Shen 8 9
Affiliations

Affiliations

  • 1 Department of Cardiovascular Medicine, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
  • 2 Shanghai Clinical Research Center for Interventional Medicine, Shanghai, 200025, China.
  • 3 Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, School of Medicine and Engineering, Beihang University, Beijing, 100191, China.
  • 4 Department of Ultrasound in Medicine, Shanghai Sixth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, China.
  • 5 Department of Ultrasound in Medicine, Shanghai Sixth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, China. yingtaomail@yeah.net.
  • 6 Department of Cardiovascular Medicine, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China. yutongwushe@163.com.
  • 7 Shanghai Clinical Research Center for Interventional Medicine, Shanghai, 200025, China. yutongwushe@163.com.
  • 8 Department of Cardiovascular Medicine, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China. rjshenying8@163.com.
  • 9 Shanghai Clinical Research Center for Interventional Medicine, Shanghai, 200025, China. rjshenying8@163.com.
  • # Contributed equally.
PMID: 38429826 DOI: 10.1186/s12951-024-02357-z
Abstract

Background: Impaired collateral formation is a major factor contributing to poor prognosis in type 2 diabetes mellitus (T2DM) patients with atherosclerotic Cardiovascular Disease. However, the current pharmacological treatments for improving collateral formation remain unsatisfactory. The induction of endothelial Autophagy and the elimination of Reactive Oxygen Species (ROS) represent potential therapeutic targets for enhancing endothelial angiogenesis and facilitating collateral formation. This study investigates the potential of molybdenum disulfide nanodots (MoS2 NDs) for enhancing collateral formation and improving prognosis.

Results: Our study shows that MoS2 NDs significantly enhance collateral formation in ischemic tissues of diabetic mice, improving effective blood resupply. Additionally, MoS2 NDs boost the proliferation, migration, and tube formation of endothelial cells under high glucose/hypoxia conditions in vitro. Mechanistically, the beneficial effects of MoS2 NDs on collateral formation not only depend on their known scavenging properties of ROS (H2O2, •O2-, and •OH) but also primarily involve a molecular pathway, cAMP/PKA-NR4A2, which promotes Autophagy and contributes to mitigating damage in diabetic endothelial cells.

Conclusions: Overall, this study investigated the specific mechanism by which MoS2 NDs mediated Autophagy activation and highlighted the synergy between Autophagy activation and antioxidation, thus suggesting that an economic and biocompatible nano-agent with dual therapeutic functions is highly preferable for promoting collateral formation in a diabetic context, thus, highlighting their therapeutic potential.

Keywords

Autophagy; Collateral formation; Molybdenum disulfide nanodots; Reactive oxygen species; Type 2 diabetes mellitus.

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