Evaluation of Nanoparticle Uptake in Tumors in Real Time Using Intravital Imaging
| Autor: | Hon-Sing Leong, Choi-Fong Cho, John D. Lewis, Andries Zijlstra, Amber Ablack |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
tumors
Pathology medicine.medical_specialty Microinjections General Chemical Engineering Comovirus Nanoparticle Chick Embryo 02 engineering and technology Polyethylene glycol confocal microscopy Chorioallantoic Membrane General Biochemistry Genetics and Molecular Biology Polyethylene Glycols law.invention 03 medical and health sciences HT29 Cells chemistry.chemical_compound Confocal microscopy law In vivo PEG ratio Image Processing Computer-Assisted medicine Animals Humans Issue 52 Fluorescent Dyes 030304 developmental biology Microscopy 0303 health sciences General Immunology and Microbiology Chemistry General Neuroscience 021001 nanoscience & nanotechnology Chorioallantoic membrane Colonic Neoplasms PEGylation Biophysics Nanoparticles Medicine intravital imaging avian embryo 0210 nano-technology |
| Zdroj: | Journal of Visualized Experiments : JoVE |
| ISSN: | 1940-087X |
| DOI: | 10.3791/2808-v |
| Popis: | Current technologies for tumor imaging, such as ultrasound, MRI, PET and CT, are unable to yield high-resolution images for the assessment of nanoparticle uptake in tumors at the microscopic level(1,2,3,) highlighting the utility of a suitable xenograft model in which to perform detailed uptake analyses. Here, we use high-resolution intravital imaging to evaluate nanoparticle uptake in human tumor xenografts in a modified, shell-less chicken embryo model. The chicken embryo model is particularly well-suited for these in vivo analyses because it supports the growth of human tumors, is relatively inexpensive and does not require anesthetization or surgery 4,5. Tumor cells form fully vascularized xenografts within 7 days when implanted into the chorioallantoic membrane (CAM)( 6). The resulting tumors are visualized by non-invasive real-time, high-resolution imaging that can be maintained for up to 72 hours with little impact on either the host or tumor systems. Nanoparticles with a wide range of sizes and formulations administered distal to the tumor can be visualized and quantified as they flow through the bloodstream, extravasate from leaky tumor vasculature, and accumulate at the tumor site. We describe here the analysis of nanoparticles derived from Cowpea mosaic virus (CPMV) decorated with near-infrared fluorescent dyes and/or polyethylene glycol polymers (PEG) (7, 8, 9,10,11). Upon intravenous administration, these viral nanoparticles are rapidly internalized by endothelial cells, resulting in global labeling of the vasculature both outside and within the tumor(7,12). PEGylation of the viral nanoparticles increases their plasma half-life, extends their time in the circulation, and ultimately enhances their accumulation in tumors via the enhanced permeability and retention (EPR) effect (7, 10,11). The rate and extent of accumulation of nanoparticles in a tumor is measured over time using image analysis software. This technique provides a method to both visualize and quantify nanoparticle dynamics in human tumors. |
| Databáze: | OpenAIRE |
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