2. Academic Validation
  3. A Mitochondrial Nanoguard Modulates Redox Homeostasis and Bioenergy Metabolism in Diabetic Peripheral Neuropathy

A Mitochondrial Nanoguard Modulates Redox Homeostasis and Bioenergy Metabolism in Diabetic Peripheral Neuropathy

  • ACS Nano. 2023 Oct 2. doi: 10.1021/acsnano.3c04462.
Yangxue Yao 1,  Xiaoyu Lei 2,  Yun Wang 1,  Geru Zhang 1,  Hongxiao Huang 1,  Yuxuan Zhao 1,  Sirong Shi 1,  Yang Gao 1,  Xiaoxiao Cai 1,  Shaojingya Gao 1,  Yunfeng Lin 1 3
Affiliations

Affiliations

  • 1 State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, P. R. China.
  • 2 Research Center for Nano Biomaterials, and Analytical & Testing Center, Sichuan University, Chengdu 610064, P. R. China.
  • 3 Sichuan Provincial Engineering Research Center of Oral Biomaterials, Chengdu, Sichuan 610041, China.
PMID: 37782570 DOI: 10.1021/acsnano.3c04462
Abstract

As a major late complication of diabetes, diabetic peripheral neuropathy (DPN) is the primary reason for amputation. Nevertheless, there are no wonder drugs available. Regulating dysfunctional mitochondria is a key therapeutic target for DPN. Resveratrol (RSV) is widely proven to guard mitochondria, yet the unsatisfactory bioavailability restricts its clinical application. Tetrahedral framework nucleic acids (tFNAs) are promising carriers due to their excellent cell entrance efficiency, biological safety, and structure editability. Here, RSV was intercalated into tFNAs to form the tFNAs-RSV complexes. tFNAs-RSV achieved enhanced stability, bioavailability, and biocompatibility compared with tFNAs and RSV alone. With its treatment, Reactive Oxygen Species (ROS) production was minimized and reductases were activated in an in vitro model of DPN. Besides, respiratory function and adenosine triphosphate (ATP) production were enhanced. tFNAs-RSV also exhibited favorable therapeutic effects on sensory dysfunction, neurovascular deterioration, demyelination, and neuroapoptosis in DPN mice. Metabolomics analysis revealed that redox regulation and energy metabolism were two principal mechanisms that were impacted during the process. Comprehensive inspections indicated that tFNAs-RSV inhibited nitrosation and oxidation and activated reductase and respiratory chain. In sum, tFNAs-RSV served as a mitochondrial nanoguard (mito-guard), representing a viable drilling target for clinical drug development of DPN.

Keywords

bioenergy metabolism; diabetic peripheral neuropathy; mitochondria; redox homeostasis; resveratrol; tetrahedral framework nucleic acids.

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