Efficiency against multidrug resistance by co-delivery of doxorubicin and curcumin with a legumain-sensitive nanocarrier
Efficiency against multidrug resistance by co-delivery of doxorubicin and curcumin with a legumain-sensitive nanocarrier
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通过使用legumain敏感纳米载体共同递送阿霉素和姜黄素来对抗多药耐药性的效率
DOI：
10.1007/s12274-017-1928-1
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发表时间：
2018-07-01
期刊：
影响因子：
9.9
通讯作者：
Nan, Kaihui
中科院分区：
文献类型：
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作者：
Lin, Sen;Xie, Peiling;Nan, Kaihui
多药耐药蛋白（MDRP）是肿瘤多药耐药的主要介导因子，是化疗成功的主要障碍。由于姜黄素（Cur）对多药耐药蛋白（MDR）的表达和功能具有抑制作用，因此制备了一种Cur和阿霉素（DOX）共递送纳米载体，通过其协同作用克服MDR肿瘤。由于豆荚蛋白在肿瘤中的过表达，DOX从该纳米载体的释放曲线被设计为豆荚蛋白调节的，这是通过用豆荚蛋白敏感肽将DOX桥连到基本材料（壳聚糖）来实现的。与单纯DOX纳米粒相比，DOX和Cur联合应用可显著抑制MCF-7/ADR细胞的多药耐药（P< 0.05），并对正常细胞（L929细胞）产生细胞毒性。这种抑制作用可归因于MCF-7/ADR细胞核中DOX积累的增加。该共递送系统通过延长循环时间、提高肿瘤靶向效率、提高抑瘤活性和抑制MDRP表达而显示出良好的抗癌作用。这些数据揭示了这种共递送系统用于癌症治疗的巨大潜力，特别是在可能发展多药耐药性的后期阶段。
Multidrug resistance proteins (MDRPs), which are implicated in the mediation of multidrug resistance in tumors, represent the main obstacle to successful chemotherapy. As curcumin (Cur) exerts inhibitory effects on both the expression and function of MDRPs, 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. Compared with nanoparticles that only contain DOX, the coadministration of DOX and Cur significantly inhibited multidrug resistance (P< 0.05) in a multidrug-resistant cancer cell model (MCF-7/ADR cell line), with cytotoxicity to normal cells (L929 cell line). Such inhibition could be ascribed to the increased DOX accumulation in the MCF-7/ADR nucleus. 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.