Development of a novel folate-modified nanobubbles with improved targeting ability to tumor cells
Development of a novel folate-modified nanobubbles with improved targeting ability to tumor cells
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DOI：
10.1016/j.ultsonch.2017.01.013
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发表时间：
2017-07-01
影响因子：
8.4
通讯作者：
Li, Jie
中科院分区：
文献类型：
--
作者：
Duan, Sujuan;Guo, Lu;Li, Jie
叶酸（FOL）与纳米泡的缀合可以增强对表达高水平叶酸受体（FR）的肿瘤的选择性靶向。为了进一步提高FOL-modified nanobubble的选择性靶向能力，通过基于脂质稳定的全氟丙烷的机械振荡和低速离心的方法，合成了具有增加的FOL含量（通过每个DSPE-PEG 2000链连接两个FOL分子来实现）的新型FOL-targeted nanobubble（（FOL）（2）-NB）。用动态光散射法（DLS）测定了气泡的大小和分布范围。使用定制的琼脂糖模具与临床US成像系统，在机械指数高达0.12，中心频率为9.0 MHz下，评价增强的成像能力。还分别通过荧光激活细胞分选（FACS）和荧光显微镜在过表达FR的人乳腺癌MCF-7细胞中进行靶向能力。成功地制备了粒径为286.87 ± 22.96 nm的（FOL）（2）-NB，它们表现出优越的上级对比成像效果。FACS和荧光显微镜研究显示，（FOL）（2）-NB组的细胞靶向能力比非靶向-NB（无FOL靶向纳米泡）和FOL-NB（每个DSPE-PEG 2000链一个FOL分子）的对照组更强。这些结果表明，通过增加每个DSPE-PEG 2000链的FOL含量，成功地制备了一种新型的更强靶向的纳米气泡。这种新的（FOL）（2）-NBs可能用于超声分子成像和FR阳性肿瘤的治疗，值得进一步研究。(C)2017爱思唯尔B. V.保留所有权利。
Conjugation of folate (FOL) to nanobubbles could enhance the selective targeting to tumors expressing high levels of folate receptor (FR). To further improve the selective targeting ability of FOL-modified nanobubbles, a novel FOL-targeted nanobubble ((FOL)(2)-NB) with increasing FOL content (accomplished by linking two FOL molecules per DSPE-PEG2000 chain) was synthesized, through the methods of mechanical shaking and low-speed centrifugation based on lipid-stabilized perfluoropropane. The bubble size and distribution range were measured by dynamic light scattering (DLS). Enhanced imaging ability was evaluated using a custom-made agarose mold with a clinical US imaging system at mechanical indices of up to 0.12 at a center frequency of 9.0 MHz. Targeted ability was also carried out in human breast cancer MCF-7 cells, which over-express the FR, by fluorescence activated cell sorting (FACS) and fluorescence microscopy, respectively. (FOL)(2)-NB with a particle size of 286.87 +/- 22.96 nm were successfully prepared, and they exhibited superior contrast imaging effect. FACS and fluorescence microscopy studies showed greater cellular targeting ability in the group of (FOL)(2)-NB than in their control group of Non-targeted-NB (no FOL targeted nanobubbles) and FOL-NB (one FOL molecule per DSPE-PEG2000 chain). These results suggest that a new type of stronger targeted nanobubble was successfully prepared by increasing the FOL content per DSPE-PEG2000 chain. This novel (FOL)(2)-NBs are potentially useful for ultrasound molecular imaging and treatment of FR-positive tumors and are worthy for further investigation. (C) 2017 Elsevier B.V. All rights reserved.