Pourjavadi Ali, Tehrani Zahra Mazaheri, Moghanaki Azardokht Abedin
Polymer Research Laboratory, Department of Chemistry, Sharif University of Technology, Azadi Avenue, P.O.Box 11365-9516, Tehran, Iran.
Pharm Res. 2016 Feb;33(2):417-32. doi: 10.1007/s11095-015-1799-7. Epub 2015 Oct 5.
The prime end of this study was to design a novel pH-sensitive as well as a PEGylated dendritic nanocarrier for both controllable and traceable gemcitabine delivery to cancerous cells. To accomplish this goal, we took advantage of a hybrid of nanoparticles including: mesoporous silica, graphene oxide and magnetite.
The nanocarrier was prepared in a multi-step synthesis route. First, magnetite mesoporous silica was deposited on the graphene oxide matrix. Then, polyamidoamine dendrimers (up to generation 1.5) with pentaethylene hexamine end groups were grafted on the surface of the nanoparticles. In order to enhance the biostability, and as the next step, the nanocarrier was modified by polyethylene glycol. Finally, these particles were functionalized by folic acid as tumor targeting agents.
According to the dynamic light scattering results, the hydrodynamic diameter of magnetic mesoporous silica graphene oxide hybrid nanoparticle was 152 ± 3 nm, while for the supramolecular hybrid nanoparticles it was about 324 ± 12 nm. Attained through the adsorption branch, the average pore diameter of these nanoparticles was 7.6 nm. Zeta potential test indicated -27.1 mV value for hybrid nanoparticles and +7.35 mV for supramolecular hybrid nanoparticles. Besides, cytotoxicity assay showed enhanced cytotoxicity of epidermoid carcinoma cell line A431 in the presence of folate conjugated carriers. The maximum release occurred at the pH 5.5, because the dendritic structure was in the open state rather than compact state.
The enhanced cytotoxicity of the epidermoid carcinoma cell line A431 in the presence of folate conjugated carriers, confirmed the improved cancerous cells uptake. Also, the positive surface potential would be a good property for the biological applications because the inherent negative-charged surface of cell membranes facilitates the uptake of positive particles by electrostatic interactions.
本研究的主要目的是设计一种新型的pH敏感且聚乙二醇化的树枝状纳米载体，用于将吉西他滨可控且可追踪地递送至癌细胞。为实现这一目标，我们利用了包括介孔二氧化硅、氧化石墨烯和磁铁矿在内的纳米颗粒混合物。
通过多步合成路线制备纳米载体。首先，将磁铁矿介孔二氧化硅沉积在氧化石墨烯基质上。然后，将带有五乙烯六胺端基的聚酰胺胺树枝状聚合物（最高到第1.5代）接枝到纳米颗粒表面。为提高生物稳定性，下一步用聚乙二醇对纳米载体进行修饰。最后，用叶酸作为肿瘤靶向剂对这些颗粒进行功能化。
根据动态光散射结果，磁性介孔二氧化硅氧化石墨烯混合纳米颗粒的流体动力学直径为152±3nm，而超分子混合纳米颗粒的流体动力学直径约为324±12nm。通过吸附分支测得这些纳米颗粒的平均孔径为7.6nm。zeta电位测试表明混合纳米颗粒的电位值为-27.1mV，超分子混合纳米颗粒的电位值为+7.35mV。此外，细胞毒性试验表明，在存在叶酸共轭载体的情况下，表皮样癌细胞系A431的细胞毒性增强。最大释放发生在pH 5.5时，因为树枝状结构处于开放状态而非紧凑状态。
在存在叶酸共轭载体的情况下，表皮样癌细胞系A431的细胞毒性增强，证实了癌细胞摄取的改善。而且，正表面电位对于生物应用来说是一个良好的特性，因为细胞膜固有的带负电荷表面通过静电相互作用促进了正颗粒的摄取。
