Fabrication and functional characterization of goldnanoconjugates for potential application in ovarian cancer.

Chitta Ranjan Patra, Resham Bhattacharya, Priyabrata Mukherjee
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Abstract

In this paper we report the surface modification and functional characterization of a gold nanoparticle-based drug delivery system for potential therapeutic application in ovarian cancer. It is currently recognized that nanotechnology may play a pivotal role in drug delivery by increasing efficacy and reducing toxicity of anti-cancer drugs. Here, we report the fabrication of a gold nanoparticles (AuNP) based drug delivery system consisting of folic acid (FA), mercapto-polyethylene glycol (PEG-SH) with a molecular weight of 2000 (designated as PSH2-2K or PSH) and cis-platin (CP) [Au-PSH-CP-FA] for potential therapeutic application in ovarian cancer. Fabrication is done in a three steps incubation process at room temperature (RT). The gold nanoconjugates are characterized with several physico-chemical techniques such as UV-Vis (UV-Visible spectroscopy), TEM (Transmission electron microscopy), ICP (Inductively coupled plasma) and radioactivity measurement with a scintillation counter. Attachment and release profiles of FA from the gold nanoconjugates are performed using (3)H-labelled FA ((3)H-FA). The expressions of folate receptor (FR) for ovarian cancer cell lines (OV-167, OVCAR-5), human umbilical vein endothelial cells (HUVEC) and ovarian surface epithelial (OSE) cells are determined by FACS analysis. Quantitation of platinum content in the nanoconjugates and its release profile is determined by platinum (Pt) analysis using ICP-MS. Biological functional characterization using in vitro proliferation assay demonstrates that Au-PSH-CP-FA not only retains the cytotoxic effect of CP, but it protects the normal cells from the cytotoxic insult, while enhancing the cytotoxic effect on the tumor cells. In future, this strategy may be utilized as a strategy for the treatment of ovarian cancers and may overcome the core side effect issues in anticancer therapy.

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金纳米共轭物的制备和功能表征,有望应用于卵巢癌的治疗。
在本文中,我们报告了一种基于金纳米粒子的给药系统的表面改性和功能表征,该系统有望应用于卵巢癌的治疗。目前,人们已经认识到纳米技术可以提高抗癌药物的疗效并降低其毒性,从而在给药过程中发挥关键作用。在此,我们报告了一种基于金纳米粒子(AuNP)的给药系统,该系统由叶酸(FA)、分子量为 2000 的巯基聚乙二醇(PEG-SH)(命名为 PSH2-2K 或 PSH)和顺式铂(CP)[Au-PSH-CP-FA]组成,有望应用于卵巢癌的治疗。制备过程分为三个步骤,在室温(RT)下孵育。金纳米共轭物采用多种物理化学技术进行表征,如 UV-Vis(紫外可见光谱)、TEM(透射电子显微镜)、ICP(电感耦合等离子体)和闪烁计数器的放射性测量。使用 (3)H 标记的叶酸((3)H-FA)分析了金纳米共轭物中叶酸的附着和释放情况。卵巢癌细胞系(OV-167、OVCAR-5)、人脐静脉内皮细胞(HUVEC)和卵巢表面上皮细胞(OSE)的叶酸受体(FR)的表达量通过 FACS 分析进行测定。通过使用 ICP-MS 进行铂(Pt)分析,确定纳米共轭物中铂含量的定量及其释放情况。利用体外增殖试验进行的生物功能特性分析表明,Au-PSH-CP-FA 不仅保留了 CP 的细胞毒性作用,而且还能保护正常细胞免受细胞毒性损伤,同时增强对肿瘤细胞的细胞毒性作用。未来,这种策略可作为治疗卵巢癌的一种策略,并可克服抗癌治疗中的核心副作用问题。
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来源期刊
Journal of Materials Chemistry
Journal of Materials Chemistry 工程技术-材料科学:综合
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