Department of Plastic and Reconstructive Surgery, Tissue Engineering Laboratory, First Affiliated Hospital, Shantou University Medical College, ShanTou City, Guangdong Province, China.
Arch Dermatol Res. 2012 Mar;304(2):139-44. doi: 10.1007/s00403-011-1181-5. Epub 2011 Oct 19.
Effective delivery of therapeutic agents is the most challenging hurdle in the use of RNA interference for research and in the clinic. Here, we assessed whether a short synthetic peptide, ACSSSPSKHCG (TD-1), could be transported through rat footpad (follicle-free) skin and efficiently deliver small interfering RNA (siRNA) to knock down a target gene. Fluorescence microscopy revealed that topical co-administration of FITC-labeled TD-1 and FAM-labeled siRNA distributed uniformly from the epidermis to the subcutaneous tissue of rat footpad skin. Transmission electron microscopy revealed the absence of cell-cell junctions and enlarged spaces between epithelial cells in the TD-1-treated footpad skin. TD-1 delivery of anti-GAPDH siRNA significantly reduced the level of GAPDH in 72 h. TD-1 can create a transient opening in non-follicle rat skin for delivery of siRNA and reveal a novel mechanism of transdermal delivery of TD-1 and siRNA into the epidermis for gene knockdown. The system might have potential for siRNA delivery in skin for drug therapy.
有效传递治疗剂是 RNA 干扰在研究和临床应用中最具挑战性的障碍。在这里，我们评估了一种短合成肽 ACSSSPSKHCG（TD-1）是否可以穿过大鼠足底（无毛囊）皮肤并有效地传递小干扰 RNA（siRNA）以敲低靶基因。荧光显微镜显示，局部共施用 FITC 标记的 TD-1 和 FAM 标记的 siRNA 从表皮均匀分布到大鼠足底皮肤的皮下组织。透射电子显微镜显示，TD-1 处理的足底皮肤上皮细胞之间的细胞-细胞连接缺失且间隙增大。TD-1 传递抗 GAPDH siRNA 可显著降低 GAPDH 在 72 小时的水平。TD-1 可在非毛囊大鼠皮肤中产生瞬时开口，用于递送 siRNA，并揭示了一种将 TD-1 和 siRNA 经皮递送至表皮以进行基因敲低的新型透皮传递机制。该系统可能有潜力用于皮肤中的 siRNA 递送来进行药物治疗。
