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High-resolution, serial intravital microscopic imaging of nanoparticle delivery and targeting in a small animal tumor model

Paper ID Volume ID Publish Year Pages File Format Full-Text
32139 44904 2013 12 PDF Available
Title
High-resolution, serial intravital microscopic imaging of nanoparticle delivery and targeting in a small animal tumor model
Abstract

SummaryNanoparticles are under active investigation for the detection and treatment of cancer. Yet our understanding of nanoparticle delivery to tumors is limited by our ability to observe the uptake process on its own scale in living subjects. We chose to study single-walled carbon nanotubes (SWNTs) because they exhibit among the highest levels of tumor uptake across the wide variety of available nanoparticles. We target them using RGD (arginine-glycine-aspartic acid) peptide which directs them to integrins overexpressed on tumor vasculature and on the surface of some tumor cells (e.g., U87MG as used here). We employ intravital microscopy (IVM) to quantitatively examine the spatiotemporal framework of targeted SWNT uptake in a murine tumor model. IVM provided a dynamic microscale window into nanoparticle circulation, binding to tumor blood vessels, extravasation, binding to tumor cells, and tumor retention. RGD-SWNTs bound to tumor vasculature significantly more than controls (P < 0.0001). RGD-SWNTs extravasated similarly compared to control RAD-SWNTs, but post-extravasation we observed as RGD-SWNTs eventually bound to individual tumor cells significantly more than RAD-SWNTs (P < 0.0001) over time. RGD-SWNTs and RAD-SWNTs displayed similar signal in tumor for a week, but over time their curves significantly diverged (P < 0.001) showing increasing RGD-SWNTs relative to untargeted SWNTs. We uncovered the complex spatiotemporal interplay between these competing uptake mechanisms. Specific uptake was delimited to early (1–6 h) and late (1–4 weeks) time-points, while non-specific uptake dominated from 6 h to 1 week. Our analysis revealed critical, quantitative insights into the dynamic, multifaceted mechanisms implicated in ligand-targeted SWNT accumulation in tumor using real-time microscopic observation.

Graphical abstract.Figure optionsDownload full-size imageDownload high-quality image (295 K)Download as PowerPoint slideHighlights► Quantitatively de-convoluted carbon nanotube targeting to tumors in live mice. ► Microscale visualization of targeting from injection to cell binding to clearance. ► Identified characteristic framework underlying nanoparticle targeting to tumors. ► Determined how targeting ligands lead to specificity in tumor targeting.

Keywords
Intravital microscopy; Cancer; Serial imaging; Targeting; Specificity; Single-walled carbon nanotubes; Nanoparticles
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High-resolution, serial intravital microscopic imaging of nanoparticle delivery and targeting in a small animal tumor model
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Publisher
Database: Elsevier - ScienceDirect
Journal: - Volume 8, Issue 2, April 2013, Pages 126–137
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us