Normal wound healing is a process that requires keratinocyte (KC) proliferation and migration. In chronic subcutaneous wounds, KC function is impaired, largely due to insulin resistance. Studies show that a glycosylated sphingolipid, GM3, is increased in the skin of type 2 diabetic subjects, suggesting it as a critical mediator of insulin resistance.Our lab has recently established spherical nucleic acids (SNAs), gold cores surrounded by a dense shell of highly oriented, covalently immobilized siRNA as a powerful tool for topically delivered gene suppression. Significantly, these structures can be delivered topically and do not require barrier disruption or transfection agents, exhibit remarkable stability towards nuclease degradation and decreased immunogenicity, and, to date, have caused no toxicity in cultured cells, mouse skin, or human skin equivalent models at concentrations required for effective gene knockdown.Herein, we designed SNAs to suppress expression of GM3S in immortalized mouse KCs and in C57BL/6 mice. Upon treatment of KCs with the SNAs and appropriate controls, GM3S mRNA and protein levels were reduced by over 80% (p<0.005). SNA treated cells show significantly increased migration (p<0.001) and exhibit a four-fold increased rate of proliferation (p<0.005). To test in vivo, 6mm circular wounds were made on diabetic C57BL/6 mice. Preliminary animal results indicate significantly faster wound closure and reduced GM3S expression in harvested tissues with SNA in diabetic mice compared to untreated mice or mice treated with vehicle alone. 

Topically applied spherical nucleic acids to increase the rate of wound healing in subjects with type 2 diabetes

247th National Meeting (2014)

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