Efficiency and Safety of β‑CD-(D3)7 as siRNA Carrier for Decreasing Matrix Metalloproteinase‑9 Expression and Improving Wound Healing in Diabetic Rats

• Published in: ACS applied materials & interfaces Vol. 9; no. 20; pp. 17417 - 17426
• Main Authors: Li, Na, Luo, Heng-Cong, Ren, Meng, Zhang, Li-Ming, Wang, Wei, Pan, Cheng-Lin, Yang, Li-Qun, Lao, Guo-Juan, Deng, Jun-Jie, Mai, Kai-jin, Sun, Kan, Yang, Chuan, Yan, Li
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 24.05.2017
• Subjects: Animals; Collagen; Diabetes Mellitus, Experimental; Matrix Metalloproteinase 9; Rats; RNA, Small Interfering; Wound Healing; siRNA; RNA interference; β-CD-(D3)7; matrix metalloproteinase-9; diabetic wound healing
• ISSN: 1944-8244; 1944-8252
• DOI: 10.1021/acsami.7b02809

Overexpression of matrix metalloproteinase-9 (MMP-9) is critical for diabetic chronic wounds involved in the refractory wound healing process. We aimed to develop a strategy through RNAi to decrease MMP-9 expression and improve diabetic wound healing. We had explored β-CD-(D3)7 as a gene carrier to take siRNA and effectively interfere with MMP-9 expression. It has been proven that β-CD-(D3)7 could be used as an effective siRNA delivery system. In this study, we want to know about the efficiency and safety of β-CD-(D3)7/MMP-9 siRNA for improving wound healing in diabetic rats. β-CD-(D3)­7/MMP-9 siRNA treated animals show lower levels of MMP-9 expression, which induce faster wound-close rates. Histological evaluation indicates that β-CD-(D3)­7/MMP-9 siRNA significantly increases the content of collagen around the injured tissues. The number of neutrophilic ganulocytes was significantly decreased through treatment of β-CD-(D3)­7/MMP-9 siRNA. In vivo fluorescence imaging assessment shows that β-CD-(D3)­7/MMP-9 siRNA could not cause organ damage and organ accumulation. The results suggest that β-CD-(D3)7/MMP-9 siRNA might be developed as a novel topical agent for the diabetic wounds treatment.