Enhanced penetration into 3D cell culture using two and three layered gold nanoparticles
Christopher G England,1 Thomas Priest,2 Guandong Zhang,2 Xinghua Sun,2 Dhruvinkumar N Patel,2 Lacey R McNally,3,4 Victor van Berkel,4,5 André M Gobin,2 Hermann B Frieboes1,2,41Department of Pharmacology and Toxicology, 2Department of Bioengineering, 3Department of Medicine, 4James Graham...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Dove Medical Press
2013-10-01
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| Series: | International Journal of Nanomedicine |
| Online Access: | http://www.dovepress.com/enhanced-penetration-into-3d-cell-culture-using-two-and-three-layered--a14536 |
| _version_ | 1818898008763269120 |
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| author | Engl CG Priest T Zhang G Sun X Patel DN McNally LR van Berkel V Gobin AM Frieboes HB |
| author_facet | Engl CG Priest T Zhang G Sun X Patel DN McNally LR van Berkel V Gobin AM Frieboes HB |
| author_sort | Engl |
| collection | DOAJ |
| description | Christopher G England,1 Thomas Priest,2 Guandong Zhang,2 Xinghua Sun,2 Dhruvinkumar N Patel,2 Lacey R McNally,3,4 Victor van Berkel,4,5 André M Gobin,2 Hermann B Frieboes1,2,41Department of Pharmacology and Toxicology, 2Department of Bioengineering, 3Department of Medicine, 4James Graham Brown Cancer Center, 5Department of Surgery, University of Louisville, KY, USAAbstract: Nano-scale particles sized 10–400 nm administered systemically preferentially extravasate from tumor vasculature due to the enhanced permeability and retention effect. Therapeutic success remains elusive, however, because of inhomogeneous particle distribution within tumor tissue. Insufficient tumor vascularization limits particle transport and also results in avascular hypoxic regions with non-proliferating cells, which can regenerate tissue after nanoparticle-delivered cytotoxicity or thermal ablation. Nanoparticle surface modifications provide for increasing tumor targeting and uptake while decreasing immunogenicity and toxicity. Herein, we created novel two layer gold-nanoshell particles coated with alkanethiol and phosphatidylcholine, and three layer nanoshells additionally coated with high-density-lipoprotein. We hypothesize that these particles have enhanced penetration into 3-dimensional cell cultures modeling avascular tissue when compared to standard poly(ethylene glycol) (PEG)-coated nanoshells. Particle uptake and distribution in liver, lung, and pancreatic tumor cell cultures were evaluated using silver-enhancement staining and hyperspectral imaging with dark field microscopy. Two layer nanoshells exhibited significantly higher uptake compared to PEGylated nanoshells. This multilayer formulation may help overcome transport barriers presented by tumor vasculature, and could be further investigated in vivo as a platform for targeted cancer therapies.Keywords: cancer nanotherapy, tumor hypoxia, nanovector transport |
| first_indexed | 2024-12-19T19:25:15Z |
| format | Article |
| id | doaj.art-a444e78fdc46408d9217ba36e88d293a |
| institution | Directory Open Access Journal |
| issn | 1176-9114 1178-2013 |
| language | English |
| last_indexed | 2024-12-19T19:25:15Z |
| publishDate | 2013-10-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | International Journal of Nanomedicine |
| spelling | doaj.art-a444e78fdc46408d9217ba36e88d293a2022-12-21T20:08:47ZengDove Medical PressInternational Journal of Nanomedicine1176-91141178-20132013-10-012013Issue 136033617Enhanced penetration into 3D cell culture using two and three layered gold nanoparticlesEnglCGPriest TZhang GSun XPatel DNMcNally LRvan Berkel VGobin AMFrieboes HBChristopher G England,1 Thomas Priest,2 Guandong Zhang,2 Xinghua Sun,2 Dhruvinkumar N Patel,2 Lacey R McNally,3,4 Victor van Berkel,4,5 André M Gobin,2 Hermann B Frieboes1,2,41Department of Pharmacology and Toxicology, 2Department of Bioengineering, 3Department of Medicine, 4James Graham Brown Cancer Center, 5Department of Surgery, University of Louisville, KY, USAAbstract: Nano-scale particles sized 10–400 nm administered systemically preferentially extravasate from tumor vasculature due to the enhanced permeability and retention effect. Therapeutic success remains elusive, however, because of inhomogeneous particle distribution within tumor tissue. Insufficient tumor vascularization limits particle transport and also results in avascular hypoxic regions with non-proliferating cells, which can regenerate tissue after nanoparticle-delivered cytotoxicity or thermal ablation. Nanoparticle surface modifications provide for increasing tumor targeting and uptake while decreasing immunogenicity and toxicity. Herein, we created novel two layer gold-nanoshell particles coated with alkanethiol and phosphatidylcholine, and three layer nanoshells additionally coated with high-density-lipoprotein. We hypothesize that these particles have enhanced penetration into 3-dimensional cell cultures modeling avascular tissue when compared to standard poly(ethylene glycol) (PEG)-coated nanoshells. Particle uptake and distribution in liver, lung, and pancreatic tumor cell cultures were evaluated using silver-enhancement staining and hyperspectral imaging with dark field microscopy. Two layer nanoshells exhibited significantly higher uptake compared to PEGylated nanoshells. This multilayer formulation may help overcome transport barriers presented by tumor vasculature, and could be further investigated in vivo as a platform for targeted cancer therapies.Keywords: cancer nanotherapy, tumor hypoxia, nanovector transporthttp://www.dovepress.com/enhanced-penetration-into-3d-cell-culture-using-two-and-three-layered--a14536 |
| spellingShingle | Engl CG Priest T Zhang G Sun X Patel DN McNally LR van Berkel V Gobin AM Frieboes HB Enhanced penetration into 3D cell culture using two and three layered gold nanoparticles International Journal of Nanomedicine |
| title | Enhanced penetration into 3D cell culture using two and three layered gold nanoparticles |
| title_full | Enhanced penetration into 3D cell culture using two and three layered gold nanoparticles |
| title_fullStr | Enhanced penetration into 3D cell culture using two and three layered gold nanoparticles |
| title_full_unstemmed | Enhanced penetration into 3D cell culture using two and three layered gold nanoparticles |
| title_short | Enhanced penetration into 3D cell culture using two and three layered gold nanoparticles |
| title_sort | enhanced penetration into 3d cell culture using two and three layered gold nanoparticles |
| url | http://www.dovepress.com/enhanced-penetration-into-3d-cell-culture-using-two-and-three-layered--a14536 |
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