酶响应性自组装多肽的抗肿瘤应用

In this paper, Objective:Enzymatic self-assembly(EISA) can trigger molecular self-assembly in situ. By using the overexpressed enzymes in the disease site, supramolecular materials can be formed in situ to improve the selectivity of drug molecules to tumor cells, prolong the retention in tumor cells, and improve the therapeutic effect. Compared with normal cells, cancer cells usually have abnormally high enzyme activity, which has also become a response point for EISA utilization, such as alkaline phosphatase(ALP), which is highly expressed in a variety of tumor cells. Therefore, we designed an enzyme-responsive site in Melphalan molecule, designed Melphalan-Yp, Melphalan-F\'Yp, Melphalan-F\'FYp three PDCs, named MelYp, MelF\'Yp, MelF\'FYp, respectively, to improve the selectivity of Melphalan itself, and explored its physical and chemical properties. Methods:The activity of these three peptides was screened in vitro, and the gelation properties in vitro were characterized. Results:MelF\'Yp had enzyme responsiveness and cell selectivity, and self-assembly was triggered by alkaline phosphatase. Conclusion:MelF\'Yp can selectively kill tumor cells with further research.