一种Legumain响应分步释放阿霉素/姜黄素缓释的纳米制剂的制备方法及应用,用肿瘤组织高表达Legumain的生物学特性,制备Legumain响应的纳米凝胶,从而实现对肿瘤组织的双重靶向效应(主动靶向和被动靶向),减少阿霉素对正常组织的次生伤害,本发明制备的纳米制剂能使药物和抑制剂先后释放功能,进入细胞后,抑制剂先从载体中释放,占据耐药蛋白活性位点,再使药物释放,这样就能最大程度减少药物外排,逆转多耐药性。

A nanocarrier for the co-delivery of Cur and doxorubicin (DOX) was prepared to overcome MDR tumors through their synergistic effects. Owing to the overexpression of legumain in tumors, the release profile of DOX from this nanocarrier was designed to be legumain modulated, which was achieved by bridging DOX to a basic material (chitosan) with a legumain sensitive peptide. The co-delivery system exhibited good anticancer effects through prolonged circulation time, improved tumor-targeting efficiency, elevation of the tumor inhibition activity, and the suppression of MDRP expression. These data revealed the enormous potential of this co-delivery system for cancer therapy, especially in the later stages where multidrug resistance may develop.