Cell-Penetrating Delivery of Nitric Oxide by Biocompatible Dinitrosyl Iron Complex and Its Dermato-Physiological Implications
After the discovery of endogenous dinitrosyl iron complexes (DNICs) as a potential biological equivalent of nitric oxide (NO), bioinorganic engineering of [Fe(NO)<sub>2</sub>] unit has emerged to develop biomimetic DNICs [(NO)<sub>2</sub>Fe(L)<sub>2</sub>] as a ch...
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MDPI AG
2021-09-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/18/10101 |
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| author | Yu-Chieh Chen Yi-Hong Chen Han Chiu Yi-Hsuan Ko Ruei-Ting Wang Wei-Ping Wang Yung-Jen Chuang Chieh-Cheng Huang Tsai-Te Lu |
| author_facet | Yu-Chieh Chen Yi-Hong Chen Han Chiu Yi-Hsuan Ko Ruei-Ting Wang Wei-Ping Wang Yung-Jen Chuang Chieh-Cheng Huang Tsai-Te Lu |
| author_sort | Yu-Chieh Chen |
| collection | DOAJ |
| description | After the discovery of endogenous dinitrosyl iron complexes (DNICs) as a potential biological equivalent of nitric oxide (NO), bioinorganic engineering of [Fe(NO)<sub>2</sub>] unit has emerged to develop biomimetic DNICs [(NO)<sub>2</sub>Fe(L)<sub>2</sub>] as a chemical biology tool for controlled delivery of NO. For example, water-soluble DNIC [Fe<sub>2</sub>(μ-SCH<sub>2</sub>CH<sub>2</sub>OH)<sub>2</sub>(NO)<sub>4</sub>] (<b>DNIC-1</b>) 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 [Fe<sub>2</sub>(μ-SCH<sub>2</sub>CH<sub>2</sub>COOH)<sub>2</sub>(NO)<sub>4</sub>] (<b>DNIC-2</b>) and its regulatory effect/biocompatibility toward epidermal cells were investigated. Upon the treatment of <b>DNIC-2</b> to human fibroblast cells, cellular uptake of <b>DNIC-2</b> 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 <b>DNIC-2</b> rationalizes its overwhelming efficacy for intracellular delivery of NO. Moreover, NO-delivery <b>DNIC-2</b> 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 <b>DNIC-2</b> holds the potential to be a novel active ingredient for skincare products. |
| first_indexed | 2024-03-10T07:35:11Z |
| format | Article |
| id | doaj.art-c7817d7ad7d746ad8256515014f68d8d |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T07:35:11Z |
| publishDate | 2021-09-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-c7817d7ad7d746ad8256515014f68d8d2023-11-22T13:32:33ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-09-0122181010110.3390/ijms221810101Cell-Penetrating Delivery of Nitric Oxide by Biocompatible Dinitrosyl Iron Complex and Its Dermato-Physiological ImplicationsYu-Chieh Chen0Yi-Hong Chen1Han Chiu2Yi-Hsuan Ko3Ruei-Ting Wang4Wei-Ping Wang5Yung-Jen Chuang6Chieh-Cheng Huang7Tsai-Te Lu8Department of Medical Science & Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu 30013, TaiwanInstitute of Biomedical Engineering, National Tsing Hua University, Hsinchu 30013, TaiwanInstitute of Biomedical Engineering, National Tsing Hua University, Hsinchu 30013, TaiwanDepartment of Medical Science & Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu 30013, TaiwanCHLITINA Research and Development Center, CHLITINA Holding Ltd., Taipei 10073, TaiwanCHLITINA Research and Development Center, CHLITINA Holding Ltd., Taipei 10073, TaiwanDepartment of Medical Science & Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu 30013, TaiwanInstitute of Biomedical Engineering, National Tsing Hua University, Hsinchu 30013, TaiwanInstitute of Biomedical Engineering, National Tsing Hua University, Hsinchu 30013, TaiwanAfter the discovery of endogenous dinitrosyl iron complexes (DNICs) as a potential biological equivalent of nitric oxide (NO), bioinorganic engineering of [Fe(NO)<sub>2</sub>] unit has emerged to develop biomimetic DNICs [(NO)<sub>2</sub>Fe(L)<sub>2</sub>] as a chemical biology tool for controlled delivery of NO. For example, water-soluble DNIC [Fe<sub>2</sub>(μ-SCH<sub>2</sub>CH<sub>2</sub>OH)<sub>2</sub>(NO)<sub>4</sub>] (<b>DNIC-1</b>) 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 [Fe<sub>2</sub>(μ-SCH<sub>2</sub>CH<sub>2</sub>COOH)<sub>2</sub>(NO)<sub>4</sub>] (<b>DNIC-2</b>) and its regulatory effect/biocompatibility toward epidermal cells were investigated. Upon the treatment of <b>DNIC-2</b> to human fibroblast cells, cellular uptake of <b>DNIC-2</b> 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 <b>DNIC-2</b> rationalizes its overwhelming efficacy for intracellular delivery of NO. Moreover, NO-delivery <b>DNIC-2</b> 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 <b>DNIC-2</b> holds the potential to be a novel active ingredient for skincare products.https://www.mdpi.com/1422-0067/22/18/10101nitric oxidedinitrosyl iron complexcontrolled deliverywound healingcollagen deposition |
| spellingShingle | Yu-Chieh Chen Yi-Hong Chen Han Chiu Yi-Hsuan Ko Ruei-Ting Wang Wei-Ping Wang Yung-Jen Chuang Chieh-Cheng Huang Tsai-Te Lu Cell-Penetrating Delivery of Nitric Oxide by Biocompatible Dinitrosyl Iron Complex and Its Dermato-Physiological Implications International Journal of Molecular Sciences nitric oxide dinitrosyl iron complex controlled delivery wound healing collagen deposition |
| title | Cell-Penetrating Delivery of Nitric Oxide by Biocompatible Dinitrosyl Iron Complex and Its Dermato-Physiological Implications |
| title_full | Cell-Penetrating Delivery of Nitric Oxide by Biocompatible Dinitrosyl Iron Complex and Its Dermato-Physiological Implications |
| title_fullStr | Cell-Penetrating Delivery of Nitric Oxide by Biocompatible Dinitrosyl Iron Complex and Its Dermato-Physiological Implications |
| title_full_unstemmed | Cell-Penetrating Delivery of Nitric Oxide by Biocompatible Dinitrosyl Iron Complex and Its Dermato-Physiological Implications |
| title_short | Cell-Penetrating Delivery of Nitric Oxide by Biocompatible Dinitrosyl Iron Complex and Its Dermato-Physiological Implications |
| title_sort | cell penetrating delivery of nitric oxide by biocompatible dinitrosyl iron complex and its dermato physiological implications |
| topic | nitric oxide dinitrosyl iron complex controlled delivery wound healing collagen deposition |
| url | https://www.mdpi.com/1422-0067/22/18/10101 |
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