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Magnetic resonance and photoacoustic imaging of brain tumor mediated by mesenchymal stem cell labeled with multifunctional nanoparticle introduced via carotid artery injection

机译:通过颈动脉注射术用多功能纳米粒子标记的间充质纳米粒子介导的脑肿瘤磁共振和光声成像

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Objective. To evaluate the feasibility of visualizing bone marrow-derived human mesenchymal stem cells (MSCs) labeled with a gold-coated magnetic resonance (MR)-active multifunctional nanoparticle and injected via the carotid artery for assessing the extent of MSC homing in glioma-bearing mice. Materials and methods. Nanoparticles containing superparamagnetic iron oxide coated with gold (SPIO@Au) with a diameter of similar to 82 nm and maximum absorbance in the near infrared region were synthesized. Bone marrow-derived MSCs conjugated with green fluorescent protein (GFP) were successfully labeled with SPIO@Au at 4 mu g ml(-1) and injected via the internal carotid artery in six mice bearing orthotopic U87 tumors. Unlabeled MSCs were used as a control. The ability of SPIO@Au-loaded MSCs to be imaged using MR and photoacoustic (PA) imaging at t = 0 h, 2 h, 24 h, and 72 h was assessed using a 7 T Bruker Biospec experimental MR scanner and a Vevo LAZR PA imaging system with a 5 ns laser as the excitation source. Histological analysis of the brain tissue was performed 72 h after MSC injection using GFP fluorescence, Prussian blue staining, and hematoxylin-and-eosin staining. Results. MSCs labeled with SPIO@Au at 4 mu g ml(-1) did not exhibit cell death or any adverse effects on differentiation or migration. The PA signal in tumors injected with SPIO@Au-loaded MSCs was clearly more enhanced post-injection, as compared with the tumors injected with unlabeled MSCs at t = 72 h. Using the same mice, T2-weighted MR imaging results taken before injection and at t = 2 h, 24h, and 72h were consistent with the PA imaging results, showing significant hypointensity of the tumor in the presence of SPIO@Au-loaded MSCs. Histological analysis also showed co-localization of GFP fluorescence and iron, thereby confirming that SPIO@Au-labeled MSCs continue to carry their nanoparticle payloads even at 72 h after injection. Conclusions. Our results demonstrated the feasibility of tracking caro
机译:客观的。为了评估用镀金磁共振(MR) - 型多功能纳米颗粒标记的可视化骨髓衍生的人间充质干细胞(MSCs)的可行性,并通过颈动脉注射用于评估胶质瘤携带小鼠的MSC归巢的程度。材料和方法。合成含有直径与82nm的金(SPIO @ Au)涂覆的超顺磁性氧化铁的纳米颗粒合成,并且在近红外区域中合成了与82nm的最大吸光度。与绿色荧光蛋白(GFP)缀合的骨髓衍生的MSC用Spio @ Au成功用4μg(-1)标记,并通过内部颈动脉注射六只小鼠轴承原位U87肿瘤。未标记的MSCS被用作控制。使用A 7 T Bruker Biospec实验MR扫描仪和VEVO LAZR评估使用MR和光声(PA)成像进行SPIO @ AU负载MSCs成像的能力。 PA成像系统具有5 ns激光器作为激励源。使用GFP荧光,普鲁士蓝染色和苏木精 - 和嗜素染色,在MSC注射后进行72小时,进行脑组织的组织学分析。结果。用Spio @ Au标记为4μgml(-1)的MSCs没有表现出细胞死亡或对分化或迁移的任何不利影响。肿瘤中的PA信号注入SPIO @ Au-Loaded MSCs的后注射后更加提高,与在T = 72小时的肿瘤注入未标记的MSC。使用相同的小鼠,在注射前和在T = 2 H,24小时和72h之前采取的T2加权MR成像结果与PA成像结果一致,在施用SPIO @ Au-Loaded MSC的情况下显示肿瘤的显着低度。组织学分析还显示出GFP荧光和铁的共定位,从而证实SPIO @ Au标记的MSC即使在注射后72小时也继续携带其纳米颗粒有效载荷。结论。我们的结果表明跟踪Caro的可行性

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