Nanotechnology Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences , Tehran , Iran.
Department of Pharmaceutical Nanotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences , Tehran , Iran.
Pharm Dev Technol. 2019 Nov;24(9):1063-1075. doi: 10.1080/10837450.2019.1569678. Epub 2019 Aug 8.
Fulfilling the purpose of developing a NP with theragnostic capabilities, the current study describes the synthesis of an aptamer-functionalized PEG-coated SPION/mesoporous silica core-shell nanoparticle for concurrent cancer targeted therapy and magnetic resonance imaging. SPIONs were synthesized according to a thermal decomposition method and served as cores for SPION/mesoporous silica core/shell nanoparticles (MMSNs). Doxorubicin was then successfully loaded in MMSNs which were then coated with di-carboxylic acid functionalized polyethylene glycol (PEG-MMSNs). AS1411 aptamers were at the end covalently attached to NPs (APT-PEG-MMSNs). The mean diameter of synthesized NPs was about 89 nm and doxorubicin encapsulation efficacy was ≈67.47%. Results of MTT based cell cytotoxicity assay demonstrated a significantly higher toxicity profile for APT-PEG-MMSNs against MCF7 cells compared to non-decorated MMSNs, while no significant differences were spotted against NIH-3T3 cells. Meanwhile, formation of protein corona around APT-PEG-MMSNs in biological medium significantly attenuated observed cytotoxicity against MCF7 cell line. Examining NPs uptake by MCF7 cells using confocal laser scanning microscopy also confirmed superiority of APT-PEG-MMSNs over PEG-MMSNs. Finally, APT decorated NPs induced highest signal intensity reduction in T-weighted images during MRI assay. In conclusion, developed NPs may serve as promising multifunctional vehicles for simultaneous cancer targeted therapy and MRI imaging.
为了实现具有治疗诊断双重功能的 NP 的开发目的，本研究描述了一种适体功能化的聚乙二醇（PEG）包覆的超顺磁性氧化铁纳米粒子（SPION）/介孔硅核壳纳米粒子的合成，用于癌症的靶向治疗和磁共振成像（MRI）。根据热分解方法合成 SPION，并将其作为 SPION/介孔硅核壳纳米粒子（MMSNs）的核。然后，成功地将阿霉素负载于 MMSNs 中，然后用二羧酸官能化的聚乙二醇（PEG-MMSNs）对其进行包覆。最后，将 AS1411 适体通过共价键连接到纳米粒子上（APT-PEG-MMSNs）。合成的 NPs 的平均粒径约为 89nm，阿霉素包封效率约为 67.47%。MTT 基于细胞细胞毒性测定的结果表明，与未修饰的 MMSNs 相比，APT-PEG-MMSNs 对 MCF7 细胞的毒性显著更高，而对 NIH-3T3 细胞则没有显著差异。同时，在生物介质中形成的 APT-PEG-MMSNs 周围的蛋白质冠显著降低了对 MCF7 细胞系的观察到的细胞毒性。使用共聚焦激光扫描显微镜检查 MCF7 细胞对 NPs 的摄取也证实了 APT-PEG-MMSNs 优于 PEG-MMSNs。最后，APT 修饰的 NPs 在 MRI 检测中诱导 T 加权图像的信号强度降低最大。总之，开发的 NPs 可作为用于癌症靶向治疗和 MRI 成像的多功能载体。
