Finetech in Medicine Research Center, Iran University of Medical Sciences, Tehran, Iran.
Department of Medical Physics, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
J Mater Chem B. 2024 Jun 19;12(24):5957-5973. doi: 10.1039/d3tb02429f.
Doxorubicin (DOX), a chemotherapy drug, has demonstrated limited efficacy against glioblastoma, an aggressive brain tumor with resistance attributed to the blood-brain barrier (BBB). This study aims to overcome this challenge by proposing the targeted delivery of magnetic Janus nanoparticles (MJNPs) functionalized with folic acid ligands, fluorescent dye, and doxorubicin (DOX/MJNPs-FLA). The properties of these nanoparticles were comprehensively evaluated using bio-physiochemical techniques such as Fourier transform infrared (FTIR) spectroscopy, dynamic light scattering (DLS), zeta potential analysis, high-resolution transmission electron microscopy (HR-TEM), vibrating sample magnetometry (VSM), fluorescence microscopy, MTT assay, hemolysis assay, and liver enzyme level evaluation. Dual-controlled DOX release was investigated under different pH and temperature conditions. Additionally, the impact of DOX/MJNPs-FLA on apoptosis induction in tumor cells, body weight, and survival time of cancerous animals was assessed. The targeted delivery system was assessed using C6 and OLN-93 cell lines as representatives of cancerous and healthy cell lines, respectively, alongside Wistar rat tumor-bearing models. Results from Prussian blue staining and confocal microscopy tests demonstrated the effective targeted internalization of MJNPs-FLA by glioblastoma cells. Additionally, we investigated the biodistribution of the nanoparticles utilizing fluorescence imaging techniques. This enabled us to track the distribution pattern of MJNPs-FLA , shedding light on their movement and accumulation within the biological system. Furthermore, the combination of chemotherapy and magnetic hyperthermia exhibited enhanced efficacy in inducing apoptosis, as evidenced by the increase of the pro-apoptotic gene and a decrease in the anti-apoptotic gene. Remarkably, this combination treatment did not cause any hepatotoxicity. This study highlights the potential of DOX/MJNPs-FLA as carriers for therapeutic and diagnostic agents in the context of theranostic applications for the treatment of brain malignancies. Additionally, it demonstrates the promising performance of DOX/MJNPs-FLA in combination treatment through passive and active targeting.
阿霉素（DOX）是一种化疗药物，对胶质母细胞瘤的疗效有限，胶质母细胞瘤是一种侵袭性脑肿瘤，由于血脑屏障（BBB）的存在而产生耐药性。本研究旨在通过提出靶向递送叶酸配体、荧光染料和阿霉素（DOX/MJNPs-FLA）功能化的磁性 Janus 纳米粒子（MJNPs）来克服这一挑战。使用生物物理化学技术，如傅里叶变换红外（FTIR）光谱、动态光散射（DLS）、Zeta 电位分析、高分辨率透射电子显微镜（HR-TEM）、振动样品磁强计（VSM）、荧光显微镜、MTT 测定、溶血试验和肝酶水平评估等，对这些纳米粒子的性能进行了全面评估。在不同的 pH 和温度条件下，研究了双重控制 DOX 释放。此外，还评估了 DOX/MJNPs-FLA 对肿瘤细胞凋亡诱导、动物体重和癌症动物存活时间的影响。使用 C6 和 OLN-93 细胞系作为癌症和健康细胞系的代表，以及 Wistar 大鼠荷瘤模型，评估了靶向递药系统。普鲁士蓝染色和共聚焦显微镜试验的结果表明，MJNPs-FLA 被神经胶质瘤细胞有效靶向内化。此外，我们还利用荧光成像技术研究了纳米粒子的生物分布。这使我们能够跟踪 MJNPs-FLA 的分布模式，了解它们在生物系统中的运动和积累情况。此外，化疗和磁热疗的联合治疗在诱导凋亡方面表现出增强的效果，这表现在促凋亡基因的增加和抗凋亡基因的减少。值得注意的是，这种联合治疗不会引起任何肝毒性。本研究强调了 DOX/MJNPs-FLA 作为治疗和诊断剂载体在脑恶性肿瘤治疗中的治疗和诊断应用中的潜力。此外，它还展示了 DOX/MJNPs-FLA 通过被动和主动靶向在联合治疗中的有前途的性能。
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