Sahne Foozie, Mohammadi Maedeh, Najafpour Ghasem D
Biotechnology Research Laboratory, Faculty of Chemical Engineering, Babol Noushirvani University of Technology, Shariati Avenue, Babol 47148, Iran.
ACS Biomater Sci Eng. 2019 May 13;5(5):2595-2609. doi: 10.1021/acsbiomaterials.8b01628. Epub 2019 Apr 1.
Nanodrug delivery systems are considered as promising therapeutic platforms to convey drugs to tumor cells. In this study, a single layer of carboxymethylcellulose (CMC) and poly N-vinylpyrrolidone (PVP) was cross-linked through disulfide bond and deposited on graphene oxide nanoparticles (GO NPs) using layer-by-layer technique. Overexpression of folate receptors on tumor cells is a great hallmark for drug delivery systems; though the NPs were functionalized by monoclonal folic acid antibody (FA) using polyethylene glycol (PEG) as linker. The mean diameter of synthesized nanoparticles was 60 nm. Curcumin was encapsulated within CMC layer with high encapsulation capacity of 94%. In vitro investigation showed 87% curcumin release at simulated tumor environment. Curcumin loaded FA modified CMC/PVP GO NPs showed high inhibition of 76 and 81% against Saos2 and MCF7 cell lines in vitro. In vivo investigations on 4T1 bearing breast cancer mice model exhibited 76% antitumor efficiency via active targeting mechanism of folate mediated transport without any significant side effect. Immunohistochemistry and immunofluorescence analyses showed enhanced antiangiogenesis, apoptosis and tumor growth inhibition.
纳米药物递送系统被认为是将药物输送到肿瘤细胞的有前景的治疗平台。在本研究中，羧甲基纤维素（CMC）和聚N-乙烯基吡咯烷酮（PVP）的单层通过二硫键交联，并使用逐层技术沉积在氧化石墨烯纳米颗粒（GO NPs）上。肿瘤细胞上叶酸受体的过表达是药物递送系统的一个重要标志；通过使用聚乙二醇（PEG）作为连接剂，用单克隆叶酸抗体（FA）对纳米颗粒进行功能化修饰。合成纳米颗粒的平均直径为60nm。姜黄素以94%的高包封率包封在CMC层内。体外研究表明，在模拟肿瘤环境中姜黄素的释放率为87%。负载姜黄素的FA修饰的CMC/PVP GO NPs在体外对Saos2和MCF7细胞系表现出76%和81%的高抑制率。对携带4T1乳腺癌小鼠模型的体内研究显示，通过叶酸介导转运的主动靶向机制，抗肿瘤效率为76%，且无任何明显副作用。免疫组织化学和免疫荧光分析显示抗血管生成、细胞凋亡和肿瘤生长抑制增强。
