Biotechnology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Laboratory of Polymer, Faculty of Chemistry, University of Tabriz, Tabriz, Iran.
Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Int J Pharm. 2017 Mar 30;520(1-2):126-138. doi: 10.1016/j.ijpharm.2017.02.008. Epub 2017 Feb 3.
Cancer is considered to be one of the leading causes of morbidity and mortality worldwide and nanotechnology was shown to have a unique potential to enhance the therapeutic performance of anti-cancer agents. A novel dual stimuli-responsive polyethylene glycol (PEG) block copolymer was synthesized for the decoration and stabilization of gold nanoparticles (NPs) to carry multiple anti-cancer drugs, doxorubicin (DOX), methotrexate (MTX) and 6-mercaptopurine (MP). DOX, MTX and MP were successfully loaded (the loading capacity of 37%, 12%, and 49%, respectively) into the NPs by ionic interaction (DOX and MTX) and disulphide-covalent bond formation (MP) in the polymeric shell of NPs. Furthermore, the triggered drugs release ability of NPs was shown through the comparison of simulated physiological and tumor tissue environments. The enhanced efficiency of the developed NPs and their targeted performance via MTX (target ligand of folate receptors) decoration were illustrated through the various cell cytotoxicity studies such as MTT assay, DAPI staining, and flow cytometry on various cancer cell lines with different levels of folate receptors. Our proposed idea in simultaneous delivery of three cytotoxic drugs with our newly designed PEGylated gold NPs may provide promising and novel prospect in cancer therapy.
癌症被认为是全球发病率和死亡率的主要原因之一，纳米技术被证明具有独特的潜力，可以提高抗癌药物的治疗效果。本研究合成了一种新型的双重刺激响应性聚乙二醇（PEG）嵌段共聚物，用于修饰和稳定金纳米粒子（NPs），以携带多种抗癌药物，包括阿霉素（DOX）、甲氨蝶呤（MTX）和 6-巯基嘌呤（MP）。通过离子相互作用（DOX 和 MTX）和聚合物壳中形成的二硫键共价键（MP），成功地将 DOX、MTX 和 MP 负载到 NPs 中（负载能力分别为 37%、12%和 49%）。此外，通过比较模拟生理和肿瘤组织环境，展示了 NPs 的触发药物释放能力。通过在具有不同叶酸受体水平的各种癌细胞系上进行 MTT 测定、DAPI 染色和流式细胞术等各种细胞毒性研究，说明了通过 MTX（叶酸受体的靶向配体）修饰开发的 NPs 的增强效率及其靶向性能。我们提出的同时递送三种细胞毒性药物的想法，以及我们新设计的聚乙二醇化金纳米粒子，可能为癌症治疗提供有前景的新前景。
