Enzyme-Directed Assembly of Nanoparticles in Tumors Monitored by in Vivo Whole Animal Imaging and ex Vivo Super-Resolution Fluorescence Imaging

被引:99
作者
Chien, Miao-Ping [1 ]
Carlini, Andrea S. [1 ]
Hu, Dehong [3 ]
Barback, Christopher V. [2 ]
Rush, Anthony M. [1 ]
Hall, David J. [2 ]
Orr, Galya [3 ]
Gianneschi, Nathan C. [1 ]
机构
[1] Univ Calif San Diego, Dept Chem & Biochem, La Jolla, CA 92093 USA
[2] Univ Calif San Diego, Dept Radiol, La Jolla, CA 92093 USA
[3] Pacific NW Natl Lab, Environm Mol Sci Lab, Richland, WA 99354 USA
关键词
OPTICAL RECONSTRUCTION MICROSCOPY; MATRIX METALLOPROTEINASES; POLYMERIZATION; PEPTIDES; CONTRAST; PROBES; LIMIT;
D O I
10.1021/ja408182p
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
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/DMF 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 micrometer-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.
引用
收藏
页码:18710 / 18713
页数:4
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