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载多柔比星超顺磁性氧化铁/壳聚糖纳米粒的制备及其作为胶质母细胞瘤治疗一体化策略的研究

Preparation of superparamagnetic iron oxide/doxorubicin loaded chitosan nanoparticles as a promising glioblastoma theranostic tool.

机构信息

Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

Department of Modern Sciences and Technologies, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

出版信息

J Cell Physiol. 2019 Feb;234(2):1547-1559. doi: 10.1002/jcp.27019. Epub 2018 Aug 26.

DOI:10.1002/jcp.27019
PMID:30145790
Abstract

Theranostic nanoparticles (NPs) are promising for opening new windows toward personalized disease management. Using a single particle capable of both diagnosis and drug delivery, is the major benefit of such particles. In the present study, chitosan NPs were used as a dual action carrier for doxorubicin (DOX; chemotherapeutic agent) and superparamagnetic iron oxide nanoparticles (SPIONs; imaging agent). SPIONs and DOX were loaded at different concentrations within poly-l-arginine-chitosan-triphosphate matrix (ACSD) using the ionic gelation method. NPs' size were in the range of 184.33 ± 4.4 nm. Drug release analysis of DOX loaded NPs (NP-DOX) showed burst release at pH 5.5 (as in tumor environment) and slow release at pH 7.4 (physiological condition), demonstrating pH-sensitive drug release profile. NP-DOX internalization was confirmed by flowcytometry and fluorescent microscopy. Uptake process results were corroborated by accumulation of drug in the intracellular space. Iron content was evaluated by inductively coupled plasma and prussian blue staining. In vitro magnetic resonance imaging (MRI) showed a decline in T relaxation times by increasing iron concentration. MRI analysis also confirmed uptake of NPs at the optimum concentration in C6 glioma cells. In conclusion, ACSD NPs could be utilized as a promising theranostic formulation for both diagnosis and treatment of glioblastoma.

摘要

治疗诊断纳米粒子(NPs)在开启个性化疾病管理的新窗口方面具有广阔的前景。使用能够同时进行诊断和药物输送的单一粒子是此类粒子的主要优势。在本研究中,壳聚糖 NPs 被用作多柔比星(DOX;化疗药物)和超顺磁性氧化铁纳米粒子(SPIONs;成像剂)的双重作用载体。SPIONs 和 DOX 以不同浓度负载在聚-L-精氨酸-壳聚糖-三磷酸盐基质(ACSD)中,采用离子凝胶化法。NPs 的粒径在 184.33±4.4nm 范围内。载 DOX 的 NPs(NP-DOX)的药物释放分析显示在 pH 5.5(如肿瘤环境)时出现突释,在 pH 7.4(生理条件)时缓慢释放,表现出 pH 敏感的药物释放特性。通过流式细胞术和荧光显微镜证实了 NP-DOX 的内化。摄取过程的结果得到了细胞内药物积累的证实。通过电感耦合等离子体和普鲁士蓝染色评估了铁含量。体外磁共振成像(MRI)显示,随着铁浓度的增加,T1 弛豫时间的下降。MRI 分析还证实了在 C6 神经胶质瘤细胞中以最佳浓度摄取 NPs。总之,ACSD NPs 可用作诊断和治疗神经胶质瘤的有前途的治疗诊断制剂。

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