Sustained Releasable Copper and Zinc Biogenic Ions Co-Assembled in Metal-Organic Frameworks Reinforced Bacterial Eradication and Wound Mitigation in Diabetic Mice

Tarik Abdelkareem Mostafa Amer; Sathyadevi Palanisamy; Pamela Berilyn So; Priya Vijayaraghavan; Shey-Cherng Tzou; Tsai-Te Lu; Chia-Her Lin; Yun-Ming Wang

doi:10.1021/acs.bioconjchem.3c00325

Sustained Releasable Copper and Zinc Biogenic Ions Co-Assembled in Metal-Organic Frameworks Reinforced Bacterial Eradication and Wound Mitigation in Diabetic Mice

Bioconjug Chem. 2023 Sep 20;34(9):1688-1703. doi: 10.1021/acs.bioconjchem.3c00325. Epub 2023 Aug 8.

Authors

Tarik Abdelkareem Mostafa Amer^{1

2}, Sathyadevi Palanisamy^{1

2

3}, Pamela Berilyn So⁴, Priya Vijayaraghavan^{1

5}, Shey-Cherng Tzou¹, Tsai-Te Lu^{3

6

7}, Chia-Her Lin⁴, Yun-Ming Wang^{1

2}

Affiliations

¹ Department of Biological Science and Technology, Institute of Molecular Medicine and Bioengineering, College of Biological Science and Technology, National Yang Ming Chiao Tung University, 75 Bo-Ai Street, Hsinchu 300, Taiwan.
² Center for Intelligent Drug Systems and Smart Bio-devices (IDS2B), National Yang Ming Chiao Tung University, 75 Bo-Ai Street, Hsinchu 300, Taiwan.
³ Institute of Biomedical Engineering, National Tsing Hua University, Hsinchu 300, Taiwan.
⁴ Department of Chemistry, National Taiwan Normal University, Taipei City 116059, Taiwan.
⁵ Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
⁶ Department of Chemistry, National Tsing Hua University, Hsinchu 300, Taiwan.
⁷ Department of Chemistry, Chung Yuan Christian University, Taoyuan 320, Taiwan.

PMID: 37552618
DOI: 10.1021/acs.bioconjchem.3c00325

Abstract

The employment of metal-organic framework (MOF)-based nanomaterials has been rapidly increasing in bioapplications owing to their biocompatibility, drug degradation, tunable porosity, and intrinsic biodegradability. This evidence suggests that the multifunctional bimetallic ions can behave as remarkable candidates for infection control and wound healing. In this study, bimetallic MOFs (Zn-HKUST-1 and FolA-Zn-HKUST-1) embedded with and without folic acid were synthesized and used for tissue sealing and repairing incisional wound sites in mice models. For comparison, HKUST-1 and FolA-HKUST-1 were also synthesized. The Brunauer-Emmett-Teller (BET) surface area measured for HKUST-1, FolA-HKUST-1, Zn-HKUST-1, and FolA-Zn-HKUST-1 from N₂ isotherms was found to be 1868, 1392, 1706, and 1179 m²/g, respectively. The measurements of contact angle values for Zn-HKUST-1, FolA-HKUST-1, and Zn-FolA-HKUST-1 were identified as 4.95 ± 0.8, 43.6 ± 3.4, and 60.62 ± 2.0°, respectively. For topical application in wound healing, they display a wide range of healing characteristics, including antibacterial and enhanced wound healing rates. In addition, in vitro cell migration and tubulogenic potentials were evaluated. The significant reduction in the wound gap and increased expression levels for CD31, eNOS, VEGF-A, and Ki67 were observed from immunohistological analyses to predict the angiogenesis behavior at the incision wound site. The wound healing rate was analyzed in the excisional dermal wounds of diabetic mice model in vivo. On account of antibacterial potentials and tissue-repairing characteristics of Cu²⁺ and Zn²⁺ ions, designing an innovative mixed metal ion-based biomaterial has wide applicability and is expected to modulate the growth of various gradient tissues.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Anti-Bacterial Agents / pharmacology
Anti-Bacterial Agents / therapeutic use
Bacteria
Copper / therapeutic use
Diabetes Mellitus, Experimental* / drug therapy
Metal-Organic Frameworks* / therapeutic use
Mice
Zinc / therapeutic use

Substances

bis(1,3,5-benzenetricarboxylate)tricopper(II)
Metal-Organic Frameworks
Copper
Zinc
Anti-Bacterial Agents