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负载银纳米颗粒的聚乳酸-羟基乙酸共聚物复合纳米颗粒通过靶向细胞表面提高重组干扰素γ的治疗效果。

Silver nanoparticle loaded PLGA composite nanoparticles for improving therapeutic efficacy of recombinant IFNγ by targeting the cell surface.

作者信息

Chaubey Nidhi, Sahoo Amaresh Kumar, Chattopadhyay Arun, Ghosh Siddhartha Sankar

机构信息

Department of Biotechnology, Indian Institute of Technology Guwahati, Guwahati, Assam 781039, India.

出版信息

Biomater Sci. 2014 Aug 30;2(8):1080-1089. doi: 10.1039/c3bm60251f. Epub 2014 Mar 11.

Abstract

The field of medical science has advanced significantly with the discoveries of new drugs and the development of sophisticated biomedical tools; still cancer therapy remains one of the major hurdles currently. Herein, we report a new approach, which exhibits complementary anti-cancer effects of recombinant IFNγ protein and silver nanoparticles (Ag NPs) when loaded together in PLGA composite NPs (GST IFNγ-Ag PLGA NPs). IFNγ acts as an antiviral and tumoricidal agent. To augment therapeutic efficacy, IFNγ was cloned, purified as GST tagged IFNγ recombinant protein, and immobilized on the composite NPs preloaded with Ag NPs. The NPs were characterized using UV-vis spectroscopy, transmission electron microscopy (TEM), field emission scanning electron microscopy (FESEM) and dynamic light scattering (DLS) analysis. Finally, the composite NPs were delivered into two different human cancer cell types, HeLa (cervical cancer) and MCF-7 (breast cancer) cells. Our results demonstrated that the recombinant IFNγ could block the cell cycle at the G1 phase and its anticancer activity could be potentiated in the presence of Ag NPs. The interaction between the recombinant IFNγ with its cell surface receptors facilitated the delivery of the composite NPs, and thus the combination of the duos ultimately led to induction of apoptosis in the cancer cells.

摘要

随着新药的发现和先进生物医学工具的开发,医学科学领域取得了显著进展;然而,癌症治疗仍然是目前的主要障碍之一。在此,我们报告一种新方法,当重组IFNγ蛋白和银纳米颗粒(Ag NPs)一起负载在聚乳酸-羟基乙酸共聚物复合纳米颗粒(GST IFNγ-Ag PLGA NPs)中时,该方法具有互补的抗癌作用。IFNγ作为一种抗病毒和杀肿瘤剂。为了提高治疗效果,IFNγ被克隆、纯化成为带有GST标签的IFNγ重组蛋白,并固定在预先负载有Ag NPs的复合纳米颗粒上。使用紫外可见光谱、透射电子显微镜(TEM)、场发射扫描电子显微镜(FESEM)和动态光散射(DLS)分析对纳米颗粒进行表征。最后,将复合纳米颗粒递送至两种不同的人类癌细胞类型,即HeLa(宫颈癌)和MCF-7(乳腺癌)细胞。我们的结果表明,重组IFNγ可在G1期阻断细胞周期,并且在存在Ag NPs的情况下其抗癌活性可增强。重组IFNγ与其细胞表面受体之间的相互作用促进了复合纳米颗粒的递送,因此二者的组合最终导致癌细胞凋亡。

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