The Mechanism Of Transdermal Peptide TD-1&Preliminary Studies On Autophagy

Transdermal delivery of drugs through the skin to the systemic circulation provides a convenient route of administration for a variety of clinical indications. Transdermal drug delivery is considered as an effective supplement to the conventional delivery routes.TD-1, a short synthetic peptide (ACSSSPSKHCG) identified by in vivo phage display, has been reported to facilitate efficient transdermal delivery of certain drugs. The transdermal peptide may create a temporary open skin barrier for macromolecular drugs to achieve the whole body blood circulation. However, the mechanisms underlying the effect of TD-1on skin barriers remain unclear, and TD-1related proteins were not determined yet.Here we proved that TD-1has a strong interaction with the Na/K-ATPase beta1subunit (ATP1B1), an abundant protein in the skin, by the yeast double hybrid experiment. The specificity of b1subunit binding was confirmed by co-immunoprecipitation and pull-down assays demonstrating TD-1binding to the cytoplasmic tail of the b1subunit. Further data indicated that this combination would affect the location of ATP1B1in skin tissues and epidermal cells, and the expression of ATP IB1in cells to some distinct. And even the interaction between TD-1and ATP1B1would have certain correlation with the transdermal function.Our experimental results firstly revealed a new potential explanation for the biological function of TD-1in enhancing transdermal delivery of drugs, which might be associated with the regulation of an essential transport protein ATP IB1. And this reveals the mechanism and principle of trandermal peptide TD-1as transdermal adjuvants and provides a solid theoretical foundation and basis for its applications. Autophagy is an evolutionally-conserved mechanism for self-regulation and response of stimulus, playing an important part in initiating and developing processes of immunity response, inflammatory reaction, cancer, cardiovascular diseases and neurodegenerative diseases. About34autophagy related proteins has been found to be involved in a related from a process, with the whites of their normal function of adjustment. Studies show that many nanomaterials and viruses have been found to be able to lead to static autophagic features.In the second part of this article, some important autophagy related proteins atg5, becnl, dram were screened through the yeast two hybrid method, and the cellular localization of the autophagy related proteins and their possible interacting partners were observed. PDMAEMA materials were found to induce certain static features of autophagy independently, accompanying with significant cell death.Our screening results revealed for the first time a few interaction candidates for autophagic proteins atg5, becnl, dram, and gave clues for their roles in the process of autophagy. Those materials caused autophagy and cell death, reflecting their functions in killing tumors. And these may point to the potential applications in adjunct chemotherapy.