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负载于叶酸共轭磁性三嵌段共聚物纳米颗粒中的双靶向替莫唑胺可提高大鼠脑胶质瘤的治疗效果。

Dual-Targeting Temozolomide Loaded in Folate-Conjugated Magnetic Triblock Copolymer Nanoparticles to Improve the Therapeutic Efficiency of Rat Brain Gliomas.

作者信息

Afzalipour Reza, Khoei Samideh, Khoee Sepideh, Shirvalilou Sakine, Jamali Raoufi Nida, Motevalian Manijeh, Karimi Mohammad Reza

机构信息

Department of Polymer Chemistry, School of Chemistry, College of Science, University of Tehran, Enghelab Street, Tehran, Iran.

出版信息

ACS Biomater Sci Eng. 2019 Nov 11;5(11):6000-6011. doi: 10.1021/acsbiomaterials.9b00856. Epub 2019 Oct 17.

Abstract

In order to conduct an effective chemotherapy session as a treatment modality for glioblastoma tumors, a nanocarrier platform is required for the drug to cross the blood brain barrier (BBB) successfully and properly target glioma cells. Dual-targeting Temozolomide (TMZ) loaded triblock polymer coated magnetic nanoparticles (MNPs) were synthesized with a SPION core and by conjugating the surface with folic acid (FA), which were shown to effectively pass the BBB and target tumor cells. Two principal methods, dynamic light scattering (DLS) and transmission electron microscopy (TEM) were employed for characterization of the synthesized nanoparticles. TMZ-loaded MNP-FA nanoparticles presented with a size of 58.61 nm, a zeta potential of -29.85 ± 0.47 mV, and a drug loading content of 6.85 ± 0.46%. Data gathered from inductively coupled plasma optical emission spectrometry (ICP-OES) and Prussian blue staining indicated effective dual-targeting, which subsequently led to an appreciably enhanced penetration through the BBB and accumulation of MNPs-FA in rat glioma cells. The anticancer effect of the dual-targeting MNPs-FA was also indicated by the increased survival time (>100%, < 0.001) and decreased tumor volume ( < 0.001). In conclusion, the dual-targeting TMZ-loaded MNPs-FA are able to improve therapeutic efficiency toward brain gliomas in rats.

摘要

为了开展有效的化疗疗程作为胶质母细胞瘤的一种治疗方式,需要一个纳米载体平台,使药物能够成功穿越血脑屏障(BBB)并精准靶向胶质瘤细胞。合成了以超顺磁性氧化铁纳米颗粒(SPION)为核心、表面偶联叶酸(FA)的双靶向载有替莫唑胺(TMZ)的三嵌段聚合物包覆磁性纳米颗粒(MNPs),结果表明其能有效穿越血脑屏障并靶向肿瘤细胞。采用动态光散射(DLS)和透射电子显微镜(TEM)这两种主要方法对合成的纳米颗粒进行表征。载有TMZ的MNP-FA纳米颗粒尺寸为58.61 nm,zeta电位为-29.85±0.47 mV,载药量为6.85±0.46%。从电感耦合等离子体发射光谱法(ICP-OES)和普鲁士蓝染色收集的数据表明了有效的双靶向作用,随后导致MNPs-FA对血脑屏障的穿透明显增强,并在大鼠胶质瘤细胞中积累。双靶向MNPs-FA的抗癌效果还表现为存活时间延长(>100%,P<0.001)和肿瘤体积减小(P<0.001)。总之,双靶向载有TMZ的MNPs-FA能够提高对大鼠脑胶质瘤的治疗效果。

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