pH and near-infrared light dual-stimuli responsive drug delivery using DNA-conjugated gold nanorods for effective treatment of multidrug resistant cancer cells.

pH and near-infrared light dual-stimuli responsive drug delivery using DNA-conjugated gold nanorods for effective treatment of multidrug resistant cancer cells.
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使用 DNA 共轭金纳米棒进行 pH 和近红外光双重刺激响应药物递送,可有效治疗多重耐药癌细胞。

DOI:
10.1016/j.jconrel.2016.04.001
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发表时间:
2016-06
期刊:
J Control Release
影响因子:
--
通讯作者:
Zhou Dejian
Zhou Dejian
中科院分区:
其他
文献类型:
--
作者:
Zhang Wenjun;Wang Feihu;Wang Yun;Wang Jining;Yu Yanna;Guo Shengrong;Chen Rongjun;Zhou Dejian

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将巯基化的pH响应性DNA偶联金纳米棒(GNR)作为多功能纳米载体用于pH和近红外(NIR)辐射双重刺激触发的靶向药物递送。通过巯基化的聚(乙二醇)-生物素进一步钝化,以通过特异性结合癌细胞过表达的生物素受体来提高其癌症靶向能力。阿霉素(DOX)是一种广泛应用于临床的抗癌药物,通过插入GNR表面的pH响应性双链DNA,可以方便地将其负载到纳米载体中,从而构建多功能纳米药物。纳米药物可以通过酸性pH环境(pH ~ 5)和/或施加808 nm NIR激光辐射来触发快速有效地释放其DOX有效载荷。与游离DOX相比,生物素修饰的纳米药物显示出极大地增加了模型多药耐药(MDR)乳腺癌细胞系(MCF-7/ADR)的细胞摄取和显著减少的药物外排。NIR辐射的应用进一步增加了DOX的释放并促进其核积累。结果,这种新的基于DNA-GNR的多功能纳米药物相对于游离DOX对MDR癌细胞的效力大大增加(约67倍)。
A thiolated pH-responsive DNA conjugated gold nanorod (GNR) was developed as a multifunctional nanocarrier for targeted, pH-and near infrared (NIR) radiation dual-stimuli triggered drug delivery. It was further passivated by a thiolated poly(ethylene glycol)-biotin to improve its cancer targeting ability by specific binding to cancer cell over-expressed biotin receptors. Doxorubicin (DOX), a widely used clinical anticancer drug, was conveniently loaded into nanocarrier by intercalating inside the double-stranded pH-responsive DNAs on the GNR surface to complete the construction of the multifunctional nanomedicine. The nanomedicine can rapidly and effectively release its DOX payload triggered by an acidic pH environment (pH ~ 5) and/or applying an 808 nm NIR laser radiation. Compared to free DOX, the biotin-modified nanomedicine displayed greatly increased cell uptake and significantly reduced drug efflux by model multidrug resistant (MDR) breast cancer cell lines (MCF-7/ADR). The application of NIR radiation further increased the DOX release and facilitated its nuclear accumulation. As a result, this new DNA-GNR based multifunctional nanomedicine exerted greatly increased potency (~ 67 fold) against the MDR cancer cells over free DOX.
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