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首页> 外文期刊>RSC Advances >A peptide-decorated and curcumin-loaded mesoporous silica nanomedicine for effectively overcoming multidrug resistance in cancer cells
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A peptide-decorated and curcumin-loaded mesoporous silica nanomedicine for effectively overcoming multidrug resistance in cancer cells

机译：肽修饰的姜黄素介孔二氧化硅纳米药物可有效克服癌细胞的多药耐药性

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Multidrug resistance (MDR) is a major obstacle to the success of cancer chemotherapy, which is closely associated with the overexpression of P-glycoprotein (P-gp) and the endolysosomal capture of drug. Therefore, to explore a strategy that could down-regulate P-gp expression and promote drugs escaping from the endolysosome is highly desired for overcoming MDR in chemotherapeutic treatment. This work reports a peptide-functionalized mesoporous silica nanomedicine (MSN) for encapsulation of curcumin (CUR) and doxorubicin (DOX) to significantly reverse the MDR in consequence of rapid endolysosomal escape and the inhibition of P-gp function. The nanomedicine is modified with the peptide of GFLGHHHRRGDS to encapsulate CUR and DOX with high loading efficiency and content. It can be selectively uptaken by the DOX resistant MCF-7/ADR cells via the specific recognition between RGDS and αvβ3 integrin to enter into lysosomes. Afterwards, the GFLG is cleaved by the lysosomal cathepsin B to release CUR and DOX from MSN. Furthermore, the imidazole-rich HHHR peptide can induce effective lysosomal membrane permeability which is beneficial for drug escape from lysosome, CUR-mediated inhibition of P-gp, and nuclear import of DOX in MCF-7/ADR cells. Confocal fluorescence imaging, flow cytometry and MTT assays demonstrate that the combination of CUR and the peptide-functionalized MSN markedly enhances the intracellular DOX concentration and achieves a successful chemotherapeutic treatment to MCF-7 or MCF-7/ADR cells, thus this work offers an effective strategy to overcome MDR.
机译：多药耐药性（MDR）是癌症化学疗法成功的主要障碍，这与P-糖蛋白（P-gp）的过表达和药物的溶酶体捕获密切相关。因此，迫切需要探索一种可以下调P-gp表达并促进从溶酶体逸出的药物的策略，以克服化学疗法中的MDR。这项工作报告了一种肽功能化的介孔二氧化硅纳米药物（MSN），用于包裹姜黄素（CUR）和阿霉素（DOX）以显着逆转MDR，这是由于快速的溶酶体逃逸和P-gp功能的抑制。用GFLGHHHRRGDS肽修饰纳米药物，以高负载效率和高含量封装CUR和DOX。通过RGDS与α v β <的特异性识别，可以被抗DOX的MCF-7 / ADR细胞 选择性摄取。 sub> 3 整合素进入溶酶体。之后，GFLG被溶酶体组织蛋白酶B裂解，从MSN释放CUR和DOX。此外，富含咪唑的HHHR肽可诱导有效的溶酶体膜通透性，有利于药物从溶酶体中逃逸，CUR介导的P-gp抑制以及DOX在MCF-7 / ADR细胞中的核导入。共聚焦荧光成像，流式细胞术和MTT分析表明，CUR和肽官能化的MSN的组合显着增强了细胞内DOX的浓度，并成功地对MCF-7或MCF-7 / ADR细胞进行了化学疗法的治疗，因此这项工作提供了克服耐多药的有效策略。

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