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首页> 外文期刊>Advanced Functional Materials >Multifunctional Molecular Beacon Micelles for Intracellular mRNA Imaging and Synergistic Therapy in Multidrug-Resistant Cancer Cells
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Multifunctional Molecular Beacon Micelles for Intracellular mRNA Imaging and Synergistic Therapy in Multidrug-Resistant Cancer Cells

机译：多功能分子信标胶束用于细胞内mRNA成像和多药耐药癌细胞的协同治疗。

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摘要

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.
机译：由P-糖蛋白（Pgp）转运蛋白的过表达引起的多药耐药性（MDR）增加了药物外排，从而限制了化学治疗的效力。期望以顺序方式同时施用MDR1基因沉默剂和化学治疗剂以在多药耐药性癌细胞中产生协同治疗作用。本文中，合理设计了基于抗MDR1分子信标（MB）的胶束（a-MBM）纳米系统。它由密集填充有MB电晕的二酰基脂质核组成。 Pgp可运输剂之一，阿霉素（DOX），被包裹在胶束的疏水核心和MB的茎序列中。 a-MBM-DOX纳米系统显示出高效的自我传递，增强的酶稳定性，出色的靶标选择性和高载药量。由于其相对较高的酶稳定性，a-MBM-DOX最初可促进细胞内MDR1 mRNA成像，以区分耐多药和非耐药的细胞，随后由于反义作用而下调MDR1基因的表达。此后，MB电晕被降解，破坏胶束纳米结构并释放DOX，由于成功恢复了药物敏感性，导致OVCAR8 / ADR细胞中DOX的高度积累和高化学治疗功效。这种胶束方法具有以连续和协同方式可视化MDR1 mRNA和克服MDR的潜力。

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  • 来源
    《Advanced Functional Materials》 |2017年第31期|1701027.1-1701027.10|共10页
  • 作者

    Zhang Ruili; Gao Shi; Wang Zhongliang; Han Da; Liu Lin; Ma Qingjie; Tan Weihong; Tian Jie; Chen Xiaoyuan;

  • 作者单位

    Jilin Univ, China Japan Union Hosp, Changchun 130033, Jilin, Peoples R China|Xidian Univ, Sch Life Sci & Technol, Minist Educ, Engn Res Ctr Mol Imaging & Neuroimaging, Xian 710126, Shaanxi, Peoples R China|Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA;

    Jilin Univ, China Japan Union Hosp, Changchun 130033, Jilin, Peoples R China;

    Xidian Univ, Sch Life Sci & Technol, Minist Educ, Engn Res Ctr Mol Imaging & Neuroimaging, Xian 710126, Shaanxi, Peoples R China;

    Univ Florida, Ctr Res Bio Nano Interface, Gainesville, FL 32611 USA;

    Jilin Univ, China Japan Union Hosp, Changchun 130033, Jilin, Peoples R China;

    Jilin Univ, China Japan Union Hosp, Changchun 130033, Jilin, Peoples R China;

    Univ Florida, Ctr Res Bio Nano Interface, Gainesville, FL 32611 USA;

    Xidian Univ, Sch Life Sci & Technol, Minist Educ, Engn Res Ctr Mol Imaging & Neuroimaging, Xian 710126, Shaanxi, Peoples R China;

    Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA;

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  • 正文语种 eng
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  • 关键词

    drug delivery; gene regulation; micelles; mRNA imaging; multidrug resistance;

    机译：药物输送;基因调控;胶束;mRNA成像;多药耐药性;

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