Enzyme-directed assembly of nanoparticles in tumors monitored by in vivo whole animal imaging and ex vivo super-resolution fluorescence imaging.
Enzyme-directed assembly of nanoparticles in tumors monitored by in vivo whole animal imaging and ex vivo super-resolution fluorescence imaging.
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DOI：
10.1021/ja408182p
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发表时间：
2013-12-18
影响因子：
15
通讯作者：
Gianneschi NC
中科院分区：
文献类型：
--
作者：
Chien MP;Carlini AS;Hu D;Barback CV;Rush AM;Hall DJ;Orr G;Gianneschi NC
在HT-1080人纤维癌肿瘤中过表达的基质金属蛋白酶用于指导异种移植小鼠模型中酶反应纳米颗粒的积累和保留。纳米颗粒是由带有简单疏水嵌段的两亲嵌段共聚物和亲水肽刷制备的胶束。用Alexa Fluor 647染料对聚合物进行末端标记，使聚合物从DMSO透析到水缓冲液时形成标记胶束。这种染料标记策略可以通过体内全动物成像和肿瘤内注射HT-1080异种移植肿瘤后的体外器官分析来观察残留物质的存在。我们认为，这种物质是通过酶诱导的积累过程被保留的，在这个过程中，颗粒从20纳米的球形胶束改变为微米级的聚集体，在动力学上将它们困在肿瘤内。通过对离体组织切片进行前所未有的超分辨率荧光分析，这一假设得到了验证，与无反应的对照组相比，颗粒大小的增加伴随着反应性颗粒的延长保留。
Matrix metalloproteinase enzymes, overexpressed in HT-1080 human fibrocarcinoma tumors, were used to guide the accumulation and retention of an enzyme-responsive nanoparticle in a xenograft mouse model. The nanoparticles were prepared as micelles from amphiphilic block copolymers bearing a simple hydrophobic block, and a hydrophilic peptide brush. The polymers were end-labeled with Alexa Fluor 647 dyes leading to the formation of labeled micelles upon dialysis of the polymers from DMSO to aqueous buffer. This dye-labeling strategy allowed the presence of the retained material to be visualized via whole animal imaging in vivo, and in ex vivo organ analysis following intratumoral injection into HT-1080 xenograft tumors. We propose that the material is retained by virtue of an enzyme-induced accumulation process whereby particles change morphology from 20 nm spherical micelles to micron-scale aggregates, kinetically trapping them within the tumor. This hypothesis is tested here via an unprecedented super resolution fluorescence analysis of ex vivo tissue slices confirming a particle size increase occurs concomitantly with extended retention of responsive particles compared to unresponsive controls.
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影响因子：
29.4
作者：
Chien, Miao-Ping;Thompson, Matthew P.;Barback, Christopher V.;Ku, Ti-Hsuan;Hall, David J.;Gianneschi, Nathan C.
通讯作者：
Gianneschi, Nathan C.
影响因子：
16.2
作者：
Dani, Adish;Huang, Bo;Bergan, Joseph;Dulac, Catherine;Zhuang, Xiaowei
通讯作者：
Zhuang, Xiaowei
影响因子：
56.9
作者：
Bates, Mark;Huang, Bo;Zhuang, Xiaowei
通讯作者：
Zhuang, Xiaowei
影响因子：
14.8
作者：
van de Linde, Sebastian;Loeschberger, Anna;Sauer, Markus
通讯作者：
Sauer, Markus
影响因子：
7.3
作者：
Galande, Amit K.;Hilderbrand, Scott A.;Tung, Ching-Hsuan
通讯作者：
Tung, Ching-Hsuan