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

England CG, Huang JS, James KT, Zhang G, Gobin AM, Frieboes HB - PLoS ONE (2015)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology & Toxicology, University of Louisville, Louisville, KY, United States of America; James Graham Brown Cancer Center, University of Louisville, Louisville, KY, United States of America.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus

Citrate gold nanoparticle and silica gold nanoshell concentrations within liver, spleen, and pancreatic tumor showed differential uptake.Bright-field visualization of tissue structure for (A) liver, (B), spleen, and (C) pancreatic tumor used to locate potential nanoparticle extravasation sites. Hyperspectral imaging of nanoparticles in combination with dark field microscopy highlights the density of extravasation sites that may affect the uptake of nanoparticles in these tissues (bars, 25 μm): (D) The liver provides numerous extravasation sites; (E) the spleen also has numerous extravasation sites, albeit to a lesser extent compared to the liver; (F) the pancreatic solid tumor has fewer sites, leading to diminished nanoparticle uptake. Bottom graph: The liver exhibited highest concentration of either citrate gold nanoparticles (black bars) or silica gold nanoshells (grey bars), followed by the spleen and the pancreatic tumor. Statistical significance is signified by (*) with a p-value < 0.05. Error bars denote standard deviation.
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pone.0129172.g007: Citrate gold nanoparticle and silica gold nanoshell concentrations within liver, spleen, and pancreatic tumor showed differential uptake.Bright-field visualization of tissue structure for (A) liver, (B), spleen, and (C) pancreatic tumor used to locate potential nanoparticle extravasation sites. Hyperspectral imaging of nanoparticles in combination with dark field microscopy highlights the density of extravasation sites that may affect the uptake of nanoparticles in these tissues (bars, 25 μm): (D) The liver provides numerous extravasation sites; (E) the spleen also has numerous extravasation sites, albeit to a lesser extent compared to the liver; (F) the pancreatic solid tumor has fewer sites, leading to diminished nanoparticle uptake. Bottom graph: The liver exhibited highest concentration of either citrate gold nanoparticles (black bars) or silica gold nanoshells (grey bars), followed by the spleen and the pancreatic tumor. Statistical significance is signified by (*) with a p-value < 0.05. Error bars denote standard deviation.

Mentions: Accumulation of nanoparticles is a function of vasculature of an organ or tissue. The liver and spleen with similar patterns of highly vascularized tissue are expected to present a higher number of nanoparticle source points, while the pancreatic tumor with a more heterogeneous vascular pattern would have less. We first used bright-field to first locate potential extravasation sites for each tissue type (Fig 7A–7C), and then switched to dark-field microscopy for analysis. Dark-field tissue sections were examined to evaluate extravasation sites within the tissue (Fig 7D–7F). Some regions of pancreatic tumor may contain large quantities of sprouting vessels due to sporadic angiogenesis, while other regions experience diminished vascular density with possibly few vessels supporting large volumes of tissue. This heterogeneity may result in tumor tissue becoming hypoxic and necrotic, with correspondingly restrained nanoparticle accumulation in these regions.


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

England CG, Huang JS, James KT, Zhang G, Gobin AM, Frieboes HB - PLoS ONE (2015)

Citrate gold nanoparticle and silica gold nanoshell concentrations within liver, spleen, and pancreatic tumor showed differential uptake.Bright-field visualization of tissue structure for (A) liver, (B), spleen, and (C) pancreatic tumor used to locate potential nanoparticle extravasation sites. Hyperspectral imaging of nanoparticles in combination with dark field microscopy highlights the density of extravasation sites that may affect the uptake of nanoparticles in these tissues (bars, 25 μm): (D) The liver provides numerous extravasation sites; (E) the spleen also has numerous extravasation sites, albeit to a lesser extent compared to the liver; (F) the pancreatic solid tumor has fewer sites, leading to diminished nanoparticle uptake. Bottom graph: The liver exhibited highest concentration of either citrate gold nanoparticles (black bars) or silica gold nanoshells (grey bars), followed by the spleen and the pancreatic tumor. Statistical significance is signified by (*) with a p-value < 0.05. Error bars denote standard deviation.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4457854&req=5

pone.0129172.g007: Citrate gold nanoparticle and silica gold nanoshell concentrations within liver, spleen, and pancreatic tumor showed differential uptake.Bright-field visualization of tissue structure for (A) liver, (B), spleen, and (C) pancreatic tumor used to locate potential nanoparticle extravasation sites. Hyperspectral imaging of nanoparticles in combination with dark field microscopy highlights the density of extravasation sites that may affect the uptake of nanoparticles in these tissues (bars, 25 μm): (D) The liver provides numerous extravasation sites; (E) the spleen also has numerous extravasation sites, albeit to a lesser extent compared to the liver; (F) the pancreatic solid tumor has fewer sites, leading to diminished nanoparticle uptake. Bottom graph: The liver exhibited highest concentration of either citrate gold nanoparticles (black bars) or silica gold nanoshells (grey bars), followed by the spleen and the pancreatic tumor. Statistical significance is signified by (*) with a p-value < 0.05. Error bars denote standard deviation.
Mentions: Accumulation of nanoparticles is a function of vasculature of an organ or tissue. The liver and spleen with similar patterns of highly vascularized tissue are expected to present a higher number of nanoparticle source points, while the pancreatic tumor with a more heterogeneous vascular pattern would have less. We first used bright-field to first locate potential extravasation sites for each tissue type (Fig 7A–7C), and then switched to dark-field microscopy for analysis. Dark-field tissue sections were examined to evaluate extravasation sites within the tissue (Fig 7D–7F). Some regions of pancreatic tumor may contain large quantities of sprouting vessels due to sporadic angiogenesis, while other regions experience diminished vascular density with possibly few vessels supporting large volumes of tissue. This heterogeneity may result in tumor tissue becoming hypoxic and necrotic, with correspondingly restrained nanoparticle accumulation in these regions.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology & Toxicology, University of Louisville, Louisville, KY, United States of America; James Graham Brown Cancer Center, University of Louisville, Louisville, KY, United States of America.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus