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Long-circulating perfluorooctyl bromide nanocapsules for tumor imaging by 19FMRI

机译:长循环全氟辛基溴化物纳米胶囊通过19FMRI进行肿瘤成像

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摘要

PLGA-PEG nanocapsules containing a liquid core of perfluorooctyl bromide were synthesized by an emulsion-evaporation process and designed as contrast agents for 19F MRI. Physico-chemical properties of plain and PEGylated nanocapsules were compared. The encapsulation efficiency of PFOB, estimated by 19F NMR spectroscopy, is enhanced when using PLGA-PEG instead of PLGA. PLGA-PEG nanocapsule diameter, measured by Dynamic Light Scattering is around 120 nm, in agreement with Transmission Electron microscopy (TEM) observations. TEM and Scanning Electron Microscopy (SEM) reveal that spherical core-shell morphology is preserved. PEGylation is further confirmed by Zeta potential measurements and X-ray Photoelectron Spectroscopy. In vitro, stealthiness of the PEGylated nanocapsules is evidenced by weak complement activation. Accumulation kinetics in the liver and the spleen was performed by 19F MRI in mice, during the first 90 min after intravenous injection. In the liver, plain nanocapsules accumulate faster than their PEGylated counterparts. We observe PEGylated nanocapsule accumulation in CT26 xenograft tumor 7 h after administration to mice, whereas plain nanocapsules remain undetectable, using 19F MRI. Our results validate the use of diblock copolymers for PEGylation to increase the residence time of nanocapsules in the blood stream and to reach tumors by the Enhanced Permeation and Retention (EPR) effect.
机译:含有全氟辛基溴化物液体核的PLGA-PEG纳米胶囊是通过乳液蒸发法合成的,并设计用作19F MRI的造影剂。比较了普通和聚乙二醇化纳米胶囊的理化性质。当使用PLGA-PEG代替PLGA时,通过19F NMR光谱估计的PFOB的封装效率会提高。通过动态光散射测量的PLGA-PEG纳米胶囊直径约为120 nm,这与透射电子显微镜(TEM)观察结果一致。 TEM和扫描电子显微镜(SEM)显示保留了球形核-壳形态。通过Zeta电位测量和X射线光电子能谱进一步证实了PEG化。在体外,通过弱补体激活证明了聚乙二醇化纳米胶囊的隐身性。在静脉注射后的最初90分钟内,通过19F MRI在小鼠体内进行肝脏和脾脏的蓄积动力学。在肝脏中,普通纳米胶囊的积累要快于其聚乙二醇化的对应胶囊。我们观察到在给予小鼠7小时后,CT26异种移植肿瘤中PEG化的纳米胶囊积聚,而使用19F MRI则无法检测到普通纳米胶囊。我们的结果验证了使用二嵌段共聚物进行PEG化,以增加纳米胶囊在血流中的停留时间,并通过增强的渗透和保留(EPR)效应到达肿瘤。

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