Cell-Penetrating Delivery of Nitric Oxide by Biocompatible Dinitrosyl Iron Complex and Its Dermato-Physiological Implications

International Journal of Molecular Sciences

Wei-Ping Wang¹  Ruei-Ting Wang¹  Yi-Hsuan Ko²  Yu-Chieh Chen²  Yung-Jen Chuang²  Han Chiu³  Chieh-Cheng Huang³  Yi-Hong Chen³  Tsai-Te Lu³ 

[1] CHLITINA Research and Development Center, CHLITINA Holding Ltd., Taipei 10073, Taiwan;Department of Medical Science & Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu 30013, Taiwan;Institute of Biomedical Engineering, National Tsing Hua University, Hsinchu 30013, Taiwan;

关键词: nitric oxide;    dinitrosyl iron complex;    controlled delivery;    wound healing;    collagen deposition;   

DOI  :  10.3390/ijms221810101

来源: DOAJ

【 摘 要 】

After the discovery of endogenous dinitrosyl iron complexes (DNICs) as a potential biological equivalent of nitric oxide (NO), bioinorganic engineering of [Fe(NO)₂] unit has emerged to develop biomimetic DNICs [(NO)₂Fe(L)₂] as a chemical biology tool for controlled delivery of NO. For example, water-soluble DNIC [Fe₂(μ-SCH₂CH₂OH)₂(NO)₄] (DNIC-1) was explored for oral delivery of NO to the brain and for the activation of hippocampal neurogenesis. However, the kinetics and mechanism for cellular uptake and intracellular release of NO, as well as the biocompatibility of synthetic DNICs, remain elusive. Prompted by the potential application of NO to dermato-physiological regulations, in this study, cellular uptake and intracellular delivery of DNIC [Fe₂(μ-SCH₂CH₂COOH)₂(NO)₄] (DNIC-2) and its regulatory effect/biocompatibility toward epidermal cells were investigated. Upon the treatment of DNIC-2 to human fibroblast cells, cellular uptake of DNIC-2 followed by transformation into protein-bound DNICs occur to trigger the intracellular release of NO with a half-life of 1.8 ± 0.2 h. As opposed to the burst release of extracellular NO from diethylamine NONOate (DEANO), the cell-penetrating nature of DNIC-2 rationalizes its overwhelming efficacy for intracellular delivery of NO. Moreover, NO-delivery DNIC-2 can regulate cell proliferation, accelerate wound healing, and enhance the deposition of collagen in human fibroblast cells. Based on the in vitro and in vivo biocompatibility evaluation, biocompatible DNIC-2 holds the potential to be a novel active ingredient for skincare products.

【 授权许可】

Unknown