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Reversing Multidrug Resistance by Multiplexed Gene Silencing for Enhanced Breast Cancer Chemotherapy
ACS Applied Materials & Interfaces ( IF 8.3 ) Pub Date : 2018-04-17 00:00:00 , DOI: 10.1021/acsami.8b02800 Yanli Li 1 , Xiaonan Gao 1 , Zhengze Yu 1 , Bo Liu 1 , Wei Pan 1 , Na Li 1 , Bo Tang 1
ACS Applied Materials & Interfaces ( IF 8.3 ) Pub Date : 2018-04-17 00:00:00 , DOI: 10.1021/acsami.8b02800 Yanli Li 1 , Xiaonan Gao 1 , Zhengze Yu 1 , Bo Liu 1 , Wei Pan 1 , Na Li 1 , Bo Tang 1
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Multidrug resistance (MDR), as one of the main problems in clinical breast cancer chemotherapy, is closely related with the over expression of drug efflux transporter P-glycoprotein (P-gp). In this study, a novel drug-loaded nanosystem was developed for inhibiting the P-gp expression and reversing MDR by multiplexed gene silencing, which composes of graphene oxide (GO) modified with two molecular beacons (MBs) and Doxorubicin (Dox). When the nanosystem was uptaken by the MDR breast cancer cells, Dox was released in the acidic endosomes and MBs were hybridized with target sequences. The intracellular multidrug resistance 1 (MDR1) mRNA and upstream erythroblastosis virus E26 oncogene homolog 1 (ETS1) mRNA can be silenced by MBs, which can effectively inhibit the expression of P-gp and further prevent the efflux of Dox and reverse MDR. In vitro and in vivo studies indicated that the strategy of reversing MDR by multiplexed gene silencing could obviously increase MCF-7/Adr cells’ Dox accumulation and enormously enhance the therapeutic efficacy of MDR breast cancer chemotherapy.
中文翻译：
通过多重基因沉默逆转多药耐药性以增强乳腺癌化疗。
作为临床乳腺癌化疗中的主要问题之一，多药耐药性与药物外排转运蛋白P-糖蛋白（P-gp）的过表达密切相关。在这项研究中，开发了一种通过多重基因沉默来抑制P-gp表达并逆转MDR的新型载药纳米系统，该系统由被两个分子信标（MBs）和阿霉素（Dox）修饰的氧化石墨烯（GO）组成。当MDR乳腺癌细胞吸收纳米系统时，Dox在酸性内体中释放，MBs与靶序列杂交。MBs可以沉默细胞内多药抗性1（MDR1）mRNA和上游成红细胞病病毒E26癌基因同源物1（ETS1）mRNA，可有效抑制P-gp的表达并进一步防止Dox的流出和逆转MDR。
更新日期：2018-04-17
中文翻译：
通过多重基因沉默逆转多药耐药性以增强乳腺癌化疗。
作为临床乳腺癌化疗中的主要问题之一，多药耐药性与药物外排转运蛋白P-糖蛋白（P-gp）的过表达密切相关。在这项研究中，开发了一种通过多重基因沉默来抑制P-gp表达并逆转MDR的新型载药纳米系统，该系统由被两个分子信标（MBs）和阿霉素（Dox）修饰的氧化石墨烯（GO）组成。当MDR乳腺癌细胞吸收纳米系统时，Dox在酸性内体中释放，MBs与靶序列杂交。MBs可以沉默细胞内多药抗性1（MDR1）mRNA和上游成红细胞病病毒E26癌基因同源物1（ETS1）mRNA，可有效抑制P-gp的表达并进一步防止Dox的流出和逆转MDR。
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