期刊
ACS APPLIED MATERIALS & INTERFACES
卷 10, 期 18, 页码 15461-15466出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsami.8b02800
关键词
multidrug resistance; multiplexed gene silencing; graphene oxide; molecular beacon; P-glycoprotein
资金
- National Natural Science Foundation of China [21390411, 21535004, 91753111, 21705098, 21775094]
- Natural Science Foundation of Shandong Province [JQ201503, ZR2015BQ003]
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据