| 초록 |
In order to enhance physical stability and flexibility of siRNA, we conjugated siRNAs to 4-arm polyethylene glycol (4PEG) via a matrix metalloproteinases (MMPs)-cleavable peptide to enhance complexation with linear polyethyleneimine (LPEI). 4PEG-siRNA/LPEI showed superior association to siRNA/LPEI at the same N/P ratio. In addition, the particle size and zeta potential of 4PEG-siRNA/LPEI were changed similarly to those of siRNA/LPEI in the presence of MMP-2 because the MMPs-cleavable linker between 4PEG and siRNA was digested by MMP-2. In diabetic ulcers, 4PEG-siRNA/LPEI was rapidly cleaved and separated to siRNA/LPEI fraction and showed higher gene silencing of MMP-2 for 14 days. By introducing 4PEG to MMP-2 siRNA, the stability and complexation efficacy were significantly enhanced and the in vivo wound healing rate was accelerated by long-term gene silencing of MMP-2, which can alter the perspective of gene therapy for successful clinical application. |
