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Multifunctional Molecular Beacon Micelles for Intracellular mRNA Imaging and Synergistic Therapy in Multidrug‐Resistant Cancer Cells
Advanced Functional Materials ( IF 18.5 ) Pub Date : 2017-05-30 , DOI: 10.1002/adfm.201701027 Ruili Zhang 1 , Shi Gao 2 , Zhongliang Wang 3 , Da Han 4 , Lin Liu 2 , Qingjie Ma 2 , Weihong Tan 4 , Jie Tian 3 , Xiaoyuan Chen 5
Advanced Functional Materials ( IF 18.5 ) Pub Date : 2017-05-30 , DOI: 10.1002/adfm.201701027 Ruili Zhang 1 , Shi Gao 2 , Zhongliang Wang 3 , Da Han 4 , Lin Liu 2 , Qingjie Ma 2 , Weihong Tan 4 , Jie Tian 3 , Xiaoyuan Chen 5
Affiliation
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Multidrug resistance (MDR) resulting from overexpression of P‐glycoprotein (Pgp) transporters increases the drug efflux and thereby limits the chemotherapeutic efficacy. It is desirable to administer both an MDR1 gene silencer and a chemotherapeutic agent in a sequential way to generate a synergistic therapeutic effect in multidrug‐resistant cancer cells. Herein, an anti‐MDR1 molecular beacon (MB)‐based micelle (a‐MBM) nanosystem is rationally designed. It is composed of a diacyllipid core densely packed with an MB corona. One of Pgp‐transportable agents, doxorubicin (DOX), is encapsulated in the hydrophobic core of the micelle and in the stem sequence of MB. The a‐MBM‐DOX nanosystem shows an efficient self‐delivery, enhanced enzymatic stability, excellent target selectivity, and high drug‐loading capacity. With its relatively high enzymatic stability, a‐MBM‐DOX initially facilitates intracellular MDR1 mRNA imaging to distinguish multidrug‐resistant and non‐multidrug‐resistant cells and subsequently downregulates the MDR1 gene expression owing to an antisense effect. After that, the MB corona is degraded, destroying the micellar nanostructure and releasing DOX, which result in a high accumulation of DOX in OVCAR8/ADR cells and a high chemotherapeutic efficacy because of successful restoration of drug sensitivity. This micelle approach has the potential for both visualizing MDR1 mRNA and overcoming MDR in a sequential and synergistic way.
中文翻译：
用于细胞内 mRNA 成像和多重耐药癌细胞协同治疗的多功能分子信标胶束
P-糖蛋白（Pgp）转运蛋白过度表达导致的多药耐药性（MDR）会增加药物外流，从而限制化疗效果。人们希望以连续的方式施用 MDR1 基因沉默剂和化疗剂，以在多重耐药癌细胞中产生协同治疗效果。在此，合理设计了一种基于抗MDR1分子信标（MB）的胶束（a-MBM）纳米系统。它由紧密堆积有 MB 冠的二酰脂核心组成。阿霉素 (DOX) 是一种 Pgp 转运剂，被封装在胶束的疏水核心和 MB 的茎序列中。a-MBM-DOX纳米系统表现出高效的自我递送、增强的酶稳定性、优异的靶点选择性和高载药能力。凭借其相对较高的酶稳定性，a-MBM-DOX 最初有利于细胞内 MDR1 mRNA 成像，以区分多重耐药和非多重耐药细胞，随后由于反义效应而下调 MDR1 基因表达。之后，MB电晕被降解，破坏胶束纳米结构并释放DOX，导致OVCAR8/ADR细胞中DOX大量积累，并因成功恢复药物敏感性而获得高化疗效果。这种胶束方法具有以连续和协同的方式可视化 MDR1 mRNA 和克服 MDR 的潜力。
更新日期：2017-05-30
中文翻译：
用于细胞内 mRNA 成像和多重耐药癌细胞协同治疗的多功能分子信标胶束
P-糖蛋白（Pgp）转运蛋白过度表达导致的多药耐药性（MDR）会增加药物外流，从而限制化疗效果。人们希望以连续的方式施用 MDR1 基因沉默剂和化疗剂，以在多重耐药癌细胞中产生协同治疗效果。在此，合理设计了一种基于抗MDR1分子信标（MB）的胶束（a-MBM）纳米系统。它由紧密堆积有 MB 冠的二酰脂核心组成。阿霉素 (DOX) 是一种 Pgp 转运剂，被封装在胶束的疏水核心和 MB 的茎序列中。a-MBM-DOX纳米系统表现出高效的自我递送、增强的酶稳定性、优异的靶点选择性和高载药能力。凭借其相对较高的酶稳定性，a-MBM-DOX 最初有利于细胞内 MDR1 mRNA 成像，以区分多重耐药和非多重耐药细胞，随后由于反义效应而下调 MDR1 基因表达。之后，MB电晕被降解，破坏胶束纳米结构并释放DOX，导致OVCAR8/ADR细胞中DOX大量积累，并因成功恢复药物敏感性而获得高化疗效果。这种胶束方法具有以连续和协同的方式可视化 MDR1 mRNA 和克服 MDR 的潜力。
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