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金纳米粒子与顺铂/阿霉素/卡培他滨偶联降低肝癌衍生癌细胞的化疗耐药性。

Gold nanoparticles conjugated with cisplatin/doxorubicin/capecitabine lower the chemoresistance of hepatocellular carcinoma-derived cancer cells.

机构信息

Department of Medicine, Division of Gastroenterology and Hepatology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.

出版信息

J Gastrointestin Liver Dis. 2012 Jun;21(2):187-96.

Abstract

BACKGROUND AND AIMS

The aim of the current study was to evaluate in vitro the anti-tumor efficacy of gold nanoparticles (GNPs) conjugated with conventional chemotherapy drugs for the treatment of liver cancer. This approach based on gold proposes a novel platform therapy with minimal toxicity and increased efficacy profiles for the destruction of hepatic cancer cells.

METHODS

GNPs, stabilized with a monolayer of L-aspartate and additional cytostatic drugs, were successfully used as a complex tumor-targeting drug-delivery system. The drugs (doxorubicin, cisplatin, and capecitabine) were non-covalently conjugated onto the hydrophilic assemblies of GNPs-L-Aspartate nanostructure. Transmission electron microscopy was used to characterize the morphological and structural properties of these drug-metallic nanostructures.

RESULTS

The cellular proliferation rates in the presence of the anti-cancer drugs delivered by the GNPs were found to be statistically lower than those of cells exposed to the cytostatic drugs alone, indicating that GNPs facilitated an increased susceptibility of cancer cells to cisplatin, doxorubicin, and capecitabine plus ribavirin.

CONCLUSION

This approach could offer a new chemotherapy strategy for patients diagnosed with unresectable hepatocellular carcinoma (HCC).

摘要

背景与目的

本研究旨在评估金纳米粒子(GNPs)与常规化疗药物偶联用于治疗肝癌的体外抗肿瘤疗效。这种基于金的方法提出了一种新的平台治疗方法,具有最小的毒性和更高的疗效,可破坏肝癌细胞。

方法

用 L-天冬氨酸单层稳定的 GNPs,并与其他细胞抑制剂药物偶联,成功用作复杂的肿瘤靶向药物递送系统。将药物(阿霉素、顺铂和卡培他滨)非共价偶联到 GNPs-L-天冬氨酸纳米结构的亲水性组装体上。透射电子显微镜用于表征这些药物-金属纳米结构的形态和结构特性。

结果

在存在由 GNPs 递送的抗癌药物的情况下,细胞增殖率明显低于单独暴露于细胞抑制剂药物的细胞,表明 GNPs 增加了癌细胞对顺铂、阿霉素和卡培他滨加利巴韦林的敏感性。

结论

这种方法可为诊断为不可切除肝细胞癌(HCC)的患者提供新的化疗策略。

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