Detection of Phosphatidylcholine-Coated Gold Nanoparticles in Orthotopic Pancreatic Adenocarcinoma using Hyperspectral Imaging

Nanoparticle uptake and distribution to solid tumors are limited by reticuloendothelial system systemic filtering and transport limitations induced by irregular intra-tumoral vascularization. Although vascular enhanced permeability and retention can aid targeting, high interstitial fluid pressure an...

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Bibliographic Details
Published in:PloS one 2015-06, Vol.10 (6), p.e0129172
Main Authors: England, Christopher G, Huang, Justin S, James, Kurtis T, Zhang, Guandong, Gobin, André M, Frieboes, Hermann B
Format: Article
Language:English
Subjects:
Ablation
Adenocarcinoma
Adenocarcinoma - metabolism
Adenocarcinoma - pathology
Animals
Biocompatibility
Bioengineering
Cell culture
Cell cycle
Cell Line, Tumor
Chemotherapy
Citric acid
Coatings
Cytotoxicity
Drug Delivery Systems - methods
Extracellular matrix
Female
Filtration
Fluid pressure
Gold
Gold - administration & dosage
Gold - chemistry
Gold - pharmacokinetics
Histology
Humans
Hyperspectral imaging
In vivo methods and tests
Lecithin
Liver
Liver - metabolism
Lung cancer
Medical imaging
Metal Nanoparticles - administration & dosage
Metal Nanoparticles - chemistry
Mice, SCID
Nanoparticles
Nanoshells - administration & dosage
Nanoshells - chemistry
Pancreas
Pancreatic cancer
Pancreatic Neoplasms - metabolism
Pancreatic Neoplasms - pathology
Particle Size
Particulates
Penetration
Permeability
Phosphatidylcholine
Phosphatidylcholines - chemistry
Phospholipids
Reticuloendothelial system
Silica
Silicon dioxide
Silicon Dioxide - administration & dosage
Silicon Dioxide - chemistry
Silicon Dioxide - pharmacokinetics
Solid tumors
Spectrophotometry - methods
Spleen
Spleen - metabolism
Tissue Distribution
Toxicity
Toxicology
Transplantation, Heterologous
Tumors
Vascularization
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Description
Summary:Nanoparticle uptake and distribution to solid tumors are limited by reticuloendothelial system systemic filtering and transport limitations induced by irregular intra-tumoral vascularization. Although vascular enhanced permeability and retention can aid targeting, high interstitial fluid pressure and dense extracellular matrix may hinder local penetration. Extravascular diffusivity depends upon nanoparticle size, surface modifications, and tissue vascularization. Gold nanoparticles functionalized with biologically-compatible layers may achieve improved uptake and distribution while enabling cytotoxicity through synergistic combination of chemotherapy and thermal ablation. Evaluation of nanoparticle uptake in vivo remains difficult, as detection methods are limited. We employ hyperspectral imaging of histology sections to analyze uptake and distribution of phosphatidylcholine-coated citrate gold nanoparticles (CGN) and silica-gold nanoshells (SGN) after tail-vein injection in mice bearing orthotopic pancreatic adenocarcinoma. For CGN, the liver and tumor showed 26.5 ± 8.2 and 23.3 ± 4.1 particles/100 μm2 within 10 μm from the nearest source and few nanoparticles beyond 50 μm, respectively. The spleen had 35.5 ± 9.3 particles/100 μm2 within 10 μm with penetration also limited to 50 μm. For SGN, the liver showed 31.1 ± 4.1 particles/100 μm2 within 10 μm of the nearest source with penetration hindered beyond 30 μm. The spleen and tumor showed uptake of 22.1 ± 6.2 and 15.8 ± 6.1 particles/100 μm2 within 10 μm, respectively, with penetration similarly hindered. CGH average concentration (nanoparticles/μm2) was 1.09 ± 0.14 in the liver, 0.74 ± 0.12 in the spleen, and 0.43 ± 0.07 in the tumor. SGN average concentration (nanoparticles/μm2) was 0.43 ± 0.07 in the liver, 0.30 ± 0.06 in the spleen, and 0.20 ± 0.04 in the tumor. Hyperspectral imaging of histology sections enables analysis of phosphatidylcholine-coated gold-based nanoparticles in pancreatic tumors with the goal to improve nanotherapeutic efficacy.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0129172