Thin Layer-Protected Gold Nanoparticles for Targeted Multimodal Imaging with Photoacoustic and CT

The large size of nanoparticles prevents rapid extravasation from blood vessels and diffusion into tumors. Multimodal imaging uses the physical properties of one modality to validate the results of another. We aim to demonstrate the use of a targeted thin layer-protected ultra-small gold nanoparticl...

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Main Authors: Jing Chen, Van Phuc Nguyen, Sangeeta Jaiswal, Xiaoyu Kang, Miki Lee, Yannis M. Paulus, Thomas D. Wang
Format: Article
Language:English
Published: MDPI AG 2021-10-01
Series:Pharmaceuticals
Subjects:
Online Access:https://www.mdpi.com/1424-8247/14/11/1075
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author Jing Chen
Van Phuc Nguyen
Sangeeta Jaiswal
Xiaoyu Kang
Miki Lee
Yannis M. Paulus
Thomas D. Wang
author_facet Jing Chen
Van Phuc Nguyen
Sangeeta Jaiswal
Xiaoyu Kang
Miki Lee
Yannis M. Paulus
Thomas D. Wang
author_sort Jing Chen
collection DOAJ
description The large size of nanoparticles prevents rapid extravasation from blood vessels and diffusion into tumors. Multimodal imaging uses the physical properties of one modality to validate the results of another. We aim to demonstrate the use of a targeted thin layer-protected ultra-small gold nanoparticles (Au-NPs) to detect cancer in vivo using multimodal imaging with photoacoustic and computed tomography (CT). The thin layer was produced using a mixed thiol-containing short ligands, including MUA, CVVVT-ol, and HS-(CH2)<sub>11</sub>-PEG<sub>4</sub>-OH. The gold nanoparticle was labeled with a heterobivalent (HB) peptide ligand that targets overexpression of epidermal growth factor receptors (EGFR) and ErbB2, hereafter HB-Au-NPs. A human xenograft model of esophageal cancer was used for imaging. HB-Au-NPs show spherical morphology, a core diameter of 4.47 ± 0.8 nm on transmission electron microscopy, and a hydrodynamic diameter of 6.41 ± 0.73 nm on dynamic light scattering. Uptake of HB-Au-NPs was observed only in cancer cells that overexpressed EGFR and ErbB2 using photoacoustic microscopy. Photoacoustic images of tumors in vivo showed peak HB-Au-NPs uptake at 8 h post-injection with systemic clearance by ~48 h. Whole-body images using CT validated specific tumor uptake of HB-Au-NPs in vivo. HB-Au-NPs showed good stability and biocompatibility with fast clearance and contrast-enhancing capability for both photoacoustic and CT imaging. A targeted thin layer-protected gold nanoprobe represents a new platform for molecular imaging and shows promise for early detection and staging of cancer.
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spelling doaj.art-4dd0ec84d7c043dda799f4eea587d48f2023-11-23T00:54:52ZengMDPI AGPharmaceuticals1424-82472021-10-011411107510.3390/ph14111075Thin Layer-Protected Gold Nanoparticles for Targeted Multimodal Imaging with Photoacoustic and CTJing Chen0Van Phuc Nguyen1Sangeeta Jaiswal2Xiaoyu Kang3Miki Lee4Yannis M. Paulus5Thomas D. Wang6Division of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USAKellogg Eye Center, Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, MI 48109, USADivision of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USADivision of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USADivision of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USAKellogg Eye Center, Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, MI 48109, USADivision of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USAThe large size of nanoparticles prevents rapid extravasation from blood vessels and diffusion into tumors. Multimodal imaging uses the physical properties of one modality to validate the results of another. We aim to demonstrate the use of a targeted thin layer-protected ultra-small gold nanoparticles (Au-NPs) to detect cancer in vivo using multimodal imaging with photoacoustic and computed tomography (CT). The thin layer was produced using a mixed thiol-containing short ligands, including MUA, CVVVT-ol, and HS-(CH2)<sub>11</sub>-PEG<sub>4</sub>-OH. The gold nanoparticle was labeled with a heterobivalent (HB) peptide ligand that targets overexpression of epidermal growth factor receptors (EGFR) and ErbB2, hereafter HB-Au-NPs. A human xenograft model of esophageal cancer was used for imaging. HB-Au-NPs show spherical morphology, a core diameter of 4.47 ± 0.8 nm on transmission electron microscopy, and a hydrodynamic diameter of 6.41 ± 0.73 nm on dynamic light scattering. Uptake of HB-Au-NPs was observed only in cancer cells that overexpressed EGFR and ErbB2 using photoacoustic microscopy. Photoacoustic images of tumors in vivo showed peak HB-Au-NPs uptake at 8 h post-injection with systemic clearance by ~48 h. Whole-body images using CT validated specific tumor uptake of HB-Au-NPs in vivo. HB-Au-NPs showed good stability and biocompatibility with fast clearance and contrast-enhancing capability for both photoacoustic and CT imaging. A targeted thin layer-protected gold nanoprobe represents a new platform for molecular imaging and shows promise for early detection and staging of cancer.https://www.mdpi.com/1424-8247/14/11/1075nanoparticlemultimodal imagingphotoacousticheterobivalent peptide
spellingShingle Jing Chen
Van Phuc Nguyen
Sangeeta Jaiswal
Xiaoyu Kang
Miki Lee
Yannis M. Paulus
Thomas D. Wang
Thin Layer-Protected Gold Nanoparticles for Targeted Multimodal Imaging with Photoacoustic and CT
Pharmaceuticals
nanoparticle
multimodal imaging
photoacoustic
heterobivalent peptide
title Thin Layer-Protected Gold Nanoparticles for Targeted Multimodal Imaging with Photoacoustic and CT
title_full Thin Layer-Protected Gold Nanoparticles for Targeted Multimodal Imaging with Photoacoustic and CT
title_fullStr Thin Layer-Protected Gold Nanoparticles for Targeted Multimodal Imaging with Photoacoustic and CT
title_full_unstemmed Thin Layer-Protected Gold Nanoparticles for Targeted Multimodal Imaging with Photoacoustic and CT
title_short Thin Layer-Protected Gold Nanoparticles for Targeted Multimodal Imaging with Photoacoustic and CT
title_sort thin layer protected gold nanoparticles for targeted multimodal imaging with photoacoustic and ct
topic nanoparticle
multimodal imaging
photoacoustic
heterobivalent peptide
url https://www.mdpi.com/1424-8247/14/11/1075
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