Divsalar Adeleh, Razmi Mahdieh, Saboury Ali Akbar, Seyedarabi Arefeh
Department of Biological Sciences, Kharazmi University, Tehran, Iran.
Anticancer Agents Med Chem. 2014;14(6):892-900. doi: 10.2174/1871520614666140207123147.
We developed a drug-delivery system comprising a novel platinum drug (Pt(II) complex) entrapped within β-Casein (β-CN) nanoparticles referred to as nano-vehicles. Fluorescence spectroscopy, UV-Vis spectrometry, dynamic light scattering (DLS), and scanning electron microscopy (SEM) were used to characterize the β-CN-Pt(II) complex . What was apparent in this study was that the solubility of Pt (II) complex increased in the presence of β-CN. Furthermore, fluorescence spectroscopy results revealed the binding of the β -CN micelle to the platinum complex at pH 7.0. The tryptophan fluorescence intensity further revealed that the optimal loading molar ratio of β-CN: Pt (II) complex was 1:3 (with β-CN at 1 mg/mL). Under these conditions, the optimal nano-vehicle was formed based on the DLS results. Results from the DLS and SEM analyses are proof for the formation of the β-CN-Pt(II) complex nanoparticles with a very good colloidal stability and an average particle size of 250 nm. Finally, the cytotoxicity of free- and encapsulated-Pt (II) complex was evaluated using colorectal carcinoma HCT116 cells, as a cancer model cell line, because platinum drugs have been used mostly for treatment of Gastrointestinal cancers. Results indicated that the cytotoxicity and cellular uptake of the drug was enhanced when entrapped in β -CN nanoparticles. Polymeric micelles are internalized into the cells via fluid-state endocytosis. These findings suggest that β-CN is an excellent nano-vehicle for targeted delivery of platinum drugs, which are generally recognized as safe (GRAS) and potentially useful in pharmaceutical industries.
我们开发了一种药物递送系统，该系统包含一种新型铂类药物（Pt(II)配合物），其包裹在被称为纳米载体的β-酪蛋白（β-CN）纳米颗粒中。采用荧光光谱法、紫外-可见光谱法、动态光散射（DLS）和扫描电子显微镜（SEM）对β-CN-Pt(II)配合物进行表征。本研究中显而易见的是，在β-CN存在的情况下，Pt(II)配合物的溶解度增加。此外，荧光光谱结果显示在pH 7.0时β-CN胶束与铂配合物发生了结合。色氨酸荧光强度进一步表明，β-CN与Pt(II)配合物的最佳负载摩尔比为1:3（β-CN浓度为1 mg/mL）。在这些条件下，根据DLS结果形成了最佳纳米载体。DLS和SEM分析结果证明形成了具有非常好的胶体稳定性且平均粒径为250 nm的β-CN-Pt(II)配合物纳米颗粒。最后，使用结直肠癌HCT116细胞作为癌症模型细胞系，评估了游离和包封的Pt(II)配合物的细胞毒性，因为铂类药物主要用于治疗胃肠道癌症。结果表明，当包封在β-CN纳米颗粒中时，药物的细胞毒性和细胞摄取增强。聚合物胶束通过液态内吞作用内化到细胞中。这些发现表明，β-CN是一种用于铂类药物靶向递送的优秀纳米载体，铂类药物通常被认为是安全的（GRAS），在制药行业具有潜在用途。
