PUBLICATION
Cell-Penetrating Delivery of Nitric Oxide by Biocompatible Dinitrosyl Iron Complex and Its Dermato-Physiological Implications
- Authors
- Chen, Y.C., Chen, Y.H., Chiu, H., Ko, Y.H., Wang, R.T., Wang, W.P., Chuang, Y.J., Huang, C.C., Lu, T.T.
- ID
- ZDB-PUB-211120-1
- Date
- 2021
- Source
- International Journal of Molecular Sciences 22(18): (Journal)
- Registered Authors
- Chuang, Yung-Jen
- Keywords
- collagen deposition, controlled delivery, dinitrosyl iron complex, nitric oxide, wound healing
- MeSH Terms
-
- Animals
- Biocompatible Materials/chemistry*
- Cell Line
- Cell Movement
- Cell Proliferation
- Cell Survival
- Collagen/chemistry
- Cornea/drug effects
- Drug Delivery Systems
- Embryo, Nonmammalian/drug effects
- Epithelium/drug effects
- Eye/drug effects
- Fibroblasts/drug effects*
- Fibroblasts/metabolism
- Humans
- In Vitro Techniques
- Iron/chemistry*
- Kinetics
- Melanocytes/metabolism
- Nitric Oxide/chemistry*
- Nitrogen Oxides/chemistry*
- Oxygen/chemistry
- Pigmentation
- Skin/drug effects*
- Wound Healing
- Zebrafish/embryology
- PubMed
- 34576264 Full text @ Int. J. Mol. Sci.
Citation
Chen, Y.C., Chen, Y.H., Chiu, H., Ko, Y.H., Wang, R.T., Wang, W.P., Chuang, Y.J., Huang, C.C., Lu, T.T. (2021) Cell-Penetrating Delivery of Nitric Oxide by Biocompatible Dinitrosyl Iron Complex and Its Dermato-Physiological Implications. International Journal of Molecular Sciences. 22(18):.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping