Doxorubicin and indocyanine green loaded superparamagnetic iron oxide nanoparticles with PEGylated phospholipid coating for magnetic resonance with fluorescence imaging and chemotherapy of glioma
Doxorubicin and indocyanine green loaded superparamagnetic iron oxide nanoparticles with PEGylated phospholipid coating for magnetic resonance with fluorescence imaging and chemotherapy of glioma
复制标题
负载阿霉素和吲哚菁绿的具有聚乙二醇化磷脂涂层的超顺磁性氧化铁纳米颗粒，用于神经胶质瘤的磁共振荧光成像和化疗
DOI：
10.2147/ijn.s173954
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发表时间：
2019-01-01
影响因子：
8
通讯作者：
Dai, Zhifei
中科院分区：
文献类型：
--
作者：
Shen, Chen;Wang, Xiaoxiong;Dai, Zhifei
背景胶质瘤是最常见的恶性脑肿瘤。由于成像方法的低灵敏度或分辨率，手术切除的结果通常不令人满意。此外，传统的化疗药物如阿霉素（DOX）的使用由于其低血脑屏障（BBB）渗透性而受到限制。最近，纳米技术的发展可以克服这些障碍。材料与方法采用热分解法制备疏水性超顺磁性氧化铁纳米粒子。使用薄膜水合方法将它们用1，2-二硬脂酰-sn-甘油基-3-磷酸乙醇胺-N-[甲氧基（聚乙二醇）-2000]（DSPE-PEG 2000）和DOX包被，然后将吲哚菁绿色（ICG）加载到磷脂层中。确定了关于NP特征的细节。采用MTT法测定其体外生物相容性和抗肿瘤活性。体内荧光和磁共振（MR）成像用于评估BBB渗透和NPs在肿瘤部位的积累。使用肿瘤大小、中位存活时间、体重和H&E染色的测量来评估抗肿瘤功效。结果制备的多功能纳米粒平均粒径为22.9 nm，zeta电位为−38.19 mV，能够提供DOX的缓释。体外实验表明，与游离DOX相比，SPIO@DSPE-PEG/DOX/ICG NP有效地增强了DOX的细胞摄取。体内荧光和MR成像显示，NPs不仅有效地穿过BBB，而且选择性地在肿瘤部位积聚。同时，在所有研究组中，用NPs治疗的C6胶质瘤大鼠表现出最大程度的治疗效果，包括最小的肿瘤体积，最低的体重减轻和最长的生存时间，没有明显的副作用。结论SPIO@DSPE-PEG/DOX/ICG纳米粒不仅可以作为磁共振和荧光双模态成像的纳米探针，还可以作为化疗药物的载体，实现脑胶质瘤的诊断治疗。
Background Glioma represents the most common malignant brain tumor. Outcomes of surgical resection are often unsatisfactory due to low sensitivity or resolution of imaging methods. Moreover, the use of traditional chemotherapeutics, such as doxorubicin (DOX), is limited due to their low blood–brain barrier (BBB) permeability. Recently, the development of nanotechnology could overcome these obstacles. Materials and methods Hydrophobic superparamagnetic iron oxide nanoparticles (SPIO NPs) were prepared with the use of thermal decomposition method. They were coated with 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (DSPE-PEG 2000) and DOX using a thin-film hydration method followed by loading of indocyanine green (ICG) into the phospholipid layers. Details regarding the characteristics of NPs were determined. The in vitro biocompatibility and antitumor efficacy were established with the use of MTT assay. In vivo fluorescence and magnetic resonance (MR) imaging were used to evaluate BBB penetration and accumulation of NPs at the tumor site. Antitumor efficacy was evaluated using measures of tumor size, median survival times, body weights, and H&E staining. Results The multifunctional NPs generated had an average diameter of 22.9 nm, a zeta potential of −38.19 mV, and were capable of providing a sustained release of DOX. In vitro experiments demonstrated that the SPIO@DSPE-PEG/DOX/ICG NPs effectively enhanced cellular uptake of DOX as compared with that of free DOX. In vivo fluorescence and MR imaging revealed that the NPs not only effectively crossed the BBB but selectively accumulated at the tumor site. Meanwhile, among all groups studied, C6 glioma-bearing rats treated with the NPs exhibited the maximal degree of therapeutic efficacy, including smallest tumor volume, lowest body weight loss, and longest survival times, with no obvious side effects. Conclusion These results suggest that the SPIO@DSPE-PEG/DOX/ICG NPs can not only function as a nanoprobe for MR and fluorescence bimodal imaging, but also as a vehicle to deliver chemotherapeutic drugs to the tumor site, to achieve the theranostic treatment of glioma.