title: Cationic star-shaped polymer as an siRNA carrier for reducing MMP-9 expression in skin fibroblast cells and promoting wound healing in diabetic rats.
abstract: BACKGROUND
  Excessive expression of matrix metalloproteinase-9 (MMP-9) is deleterious to the cutaneous wound-healing process in the context of diabetes. The aim of the present study was to explore whether a cationic star-shaped polymer consisting of β-cyclodextrin (β-CD) core and poly(amidoamine) dendron arms (β-CD-[D₃]₇) could be used as the gene carrier of small interfering RNA (siRNA) to reduce MMP-9 expression for enhanced diabetic wound healing.
  
  
  METHODS
  The cytotoxicity of β-CD-(D₃)₇ was investigated by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay (MMT) method in the rat CRL1213 skin fibroblast cell line. The transfection efficiency of β-CD-(D₃)₇/MMP-9-small interfering RNA (siRNA) complexes was determined by confocal microscopy and flow cytometry. Quantitative real time (RT) polymerase chain reaction was performed to measure the gene expression of MMP-9 after the transfection by β-CD-(D₃)₇/MMP-9-siRNA complexes. The β-CD-(D₃)₇/MMP-9-siRNA complexes were injected on the wounds of streptozocin-induced diabetic rats. Wound closure was measured on days 4 and 7 post-wounding.
  
  
  RESULTS
  β-CD-(D₃)₇ exhibited low cytotoxicity in fibroblast cells, and easily formed the complexes with MMP-9-siRNA. The β-CD-(D₃)₇/MMP-9-siRNA complexes were readily taken up by fibroblast cells, resulting in the downregulation of MMP-9 gene expression (P<0.01). Animal experiments revealed that the treatment by β-CD-(D₃)₇/MMP-9-siRNA complexes enhanced wound closure in diabetic rats on day 7 post-wounding (P<0.05).
  
  
  CONCLUSIONS
  β-CD-(D₃)₇ may be used as an efficient carrier for the delivery of MMP-9-siRNA to reduce MMP-9 expression in skin fibroblast cells and promote wound healing in diabetic rats.
authors: Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China.
authors: Na
authors: N
authors: Li
authors: Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China.
authors: Heng-Cong
authors: HC
authors: Luo
authors: Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China.
authors: Chuan
authors: C
authors: Yang
authors: DSAPM Lab and PCFM Lab, Institute of Polymer Science, Department of Polymer and Materials Science, School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou, People's Republic of China.
authors: Jun-Jie
authors: JJ
authors: Deng
authors: Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China.
authors: Meng
authors: M
authors: Ren
authors: Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China.
authors: Xiao-Ying
authors: XY
authors: Xie
authors: Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China.
authors: Diao-Zhu
authors: DZ
authors: Lin
authors: Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China.
authors: Li
authors: L
authors: Yan
authors: DSAPM Lab and PCFM Lab, Institute of Polymer Science, Department of Polymer and Materials Science, School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou, People's Republic of China.
authors: Li-Ming
authors: LM
authors: Zhang
mesh_terms: D000818:Animals; D002412:Cations / Q000737:chemistry; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental; D005347:Fibroblasts; D015870:Gene Expression; D020780:Matrix Metalloproteinase 9 / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D053758:Nanoparticles / Q000737:chemistry*; D034741:RNA, Small Interfering / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology*; D017207:Rats, Sprague-Dawley; D014162:Transfection / Q000379:methods; D014945:Wound Healing / Q000187:drug effects*; D047392:beta-Cyclodextrins / Q000737:chemistry
chemical_list: D002412:Cations; D034741:RNA, Small Interfering; D047392:beta-Cyclodextrins; D020780:Matrix Metalloproteinase 9
keywords: diabetic foot ulceration; gene carrier; matrix metalloproteinase-9; small interfering RNAs