Microscopic investigation of" topically applied nanoparticles for molecular imaging of fresh tissue surfaces.

Microscopic investigation of" topically applied nanoparticles for molecular imaging of fresh tissue surfaces.
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DOI:
10.1002/jbio.201700246
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发表时间:
2018-04
影响因子:
2.8
通讯作者:
Liu JTC
Liu JTC
中科院分区:
物理与天体物理2区
文献类型:
--
作者:
Kang S;Wang YW;Xu X;Navarro E;Tichauer KM;Liu JTC

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先前的研究表明,局部应用于新鲜组织的功能化纳米颗粒(NP)能够快速靶向癌症的细胞表面蛋白质生物标志物。此外,研究已经表明,配对试剂方法(其中非靶向NP与一组靶向NP共同施用)控制NP的非特异性行为,使得能够对生物标志物表达进行定量成像。然而,考虑到组织中靶向NP的非特异性积累、扩散和化学结合的复杂性,需要进行研究以更好地理解微观尺度上的这些过程。在这里,新鲜组织用配对试剂方法染色,冷冻并切片以成像靶向和非靶向NP的深度依赖性积累。发现靶向与非靶向NP浓度的比率-用于区分肿瘤和良性组织的参数-随着NP扩散深度的增加而减少,这是由于非特异性积累和不良洗脱。然后假设并实验证明,较大的NP将在组织表面以下表现出较少的扩散,从而实现较高的靶向与非靶向NP比率。总之,这些方法和研究使得能够设计具有改进的灵敏度和对比度的NP试剂,用于新鲜组织的快速分子成像。
Previous studies have shown that functionalized nanoparticles (NPs) topically applied on fresh tissues are able to rapidly target cell-surface protein biomarkers of cancer. Furthermore, studies have shown that a paired-agent approach, in which an untargeted NP is co-administered with a panel of targeted NPs, controls for nonspecific behavior of the NPs, enabling quantitative imaging of biomarker expression. However, given the complexities in nonspecific accumulation, diffusion, and chemical binding of targeted NPs in tissues, studies are needed to better understand these processes at the microscopic scale. Here, fresh tissues were stained with a paired-agent approach, frozen, and sectioned to image the depth-dependent accumulation of targeted and untargeted NPs. The ratio of targeted to untargeted NP concentrations – a parameter used to distinguish between tumor and benign tissues – was found to diminish with increasing NP diffusion depths due to nonspecific accumulation and poor washout. It was then hypothesized and experimentally demonstrated that larger NPs would exhibit less diffusion below tissue surfaces, enabling higher targeted to untargeted NP ratios. In summary, these methods and investigations have enabled the design of NP agents with improved sensitivity and contrast for rapid molecular imaging of fresh tissues.
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