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

Journal Article · Wed Dec 18 04:00:00 EST 2013 · Journal of the American Chemical Society, 135(50):18710-18713

DOI:https://doi.org/10.1021/ja408182p· OSTI ID:1130253

Chien, Miao-Ping; Carlini, Andrea S.; Hu, Dehong; Barback, Christopher V.; Rush, Anthony M.; Hall, David J.; Orr, Galya; Gianneschi, Nathan C.

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.

• Research Organization: Pacific Northwest National Laboratory (PNNL), Richland, WA (US), Environmental Molecular Sciences Laboratory (EMSL)
• Sponsoring Organization: USDOE
• DOE Contract Number: AC05-76RL01830
• OSTI ID: 1130253
• Report Number(s): PNNL-SA-98263; 46907; KP1704020
• Journal Information: Journal of the American Chemical Society, 135(50):18710-18713, Journal Name: Journal of the American Chemical Society, 135(50):18710-18713
• Country of Publication: United States
• Language: English

Related Subjects

Environmental Molecular Sciences Laboratory
Ex Vivo
In Vivo
Nanoparticles
super resolution fluorescence imaging
tumors