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Viral nanoparticles for in vivo tumor imaging.

作者信息

Wen Amy M, Lee Karin L, Yildiz Ibrahim, Bruckman Michael A, Shukla Sourabh, Steinmetz Nicole F

机构信息

Department of Biomedical Engineering, Case Western Reserve University.

出版信息

J Vis Exp. 2012 Nov 16(69):e4352. doi: 10.3791/4352.


DOI:10.3791/4352
PMID:23183850
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3572551/
Abstract

The use of nanomaterials has the potential to revolutionize materials science and medicine. Currently, a number of different nanoparticles are being investigated for applications in imaging and therapy. Viral nanoparticles (VNPs) derived from plants can be regarded as self-assembled bionanomaterials with defined sizes and shapes. Plant viruses under investigation in the Steinmetz lab include icosahedral particles formed by Cowpea mosaic virus (CPMV) and Brome mosaic virus (BMV), both of which are 30 nm in diameter. We are also developing rod-shaped and filamentous structures derived from the following plant viruses: Tobacco mosaic virus (TMV), which forms rigid rods with dimensions of 300 nm by 18 nm, and Potato virus X (PVX), which form filamentous particles 515 nm in length and 13 nm in width (the reader is referred to refs. (1) and (2) for further information on VNPs). From a materials scientist's point of view, VNPs are attractive building blocks for several reasons: the particles are monodisperse, can be produced with ease on large scale in planta, are exceptionally stable, and biocompatible. Also, VNPs are "programmable" units, which can be specifically engineered using genetic modification or chemical bioconjugation methods. The structure of VNPs is known to atomic resolution, and modifications can be carried out with spatial precision at the atomic level, a level of control that cannot be achieved using synthetic nanomaterials with current state-of-the-art technologies. In this paper, we describe the propagation of CPMV, PVX, TMV, and BMV in Vigna ungiuculata and Nicotiana benthamiana plants. Extraction and purification protocols for each VNP are given. Methods for characterization of purified and chemically-labeled VNPs are described. In this study, we focus on chemical labeling of VNPs with fluorophores (e.g. Alexa Fluor 647) and polyethylene glycol (PEG). The dyes facilitate tracking and detection of the VNPs, and PEG reduces immunogenicity of the proteinaceous nanoparticles while enhancing their pharmacokinetics. We demonstrate tumor homing of PEGylated VNPs using a mouse xenograft tumor model. A combination of fluorescence imaging of tissues ex vivo using Maestro Imaging System, fluorescence quantification in homogenized tissues, and confocal microscopy is used to study biodistribution. VNPs are cleared via the reticuloendothelial system (RES); tumor homing is achieved passively via the enhanced permeability and retention (EPR) effect. The VNP nanotechnology is a powerful plug-and-play technology to image and treat sites of disease in vivo. We are further developing VNPs to carry drug cargos and clinically-relevant imaging moieties, as well as tissue-specific ligands to target molecular receptors overexpressed in cancer and cardiovascular disease.

摘要

相似文献

[1]
Viral nanoparticles for in vivo tumor imaging.

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[2]
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[3]
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[4]
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[5]
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[6]
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Methods Mol Biol. 2018

[7]
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[8]
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[9]
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[10]
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引用本文的文献

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[2]
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[3]
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[4]
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[5]
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[6]
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[7]
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[8]
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[9]
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[10]
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本文引用的文献

[1]
Engineering of Brome mosaic virus for biomedical applications.

RSC Adv. 2012-5-7

[2]
Increased tumor homing and tissue penetration of the filamentous plant viral nanoparticle Potato virus X.

Mol Pharm. 2012-7-9

[3]
Intravital imaging of human prostate cancer using viral nanoparticles targeted to gastrin-releasing Peptide receptors.

Small. 2011-4-26

[4]
Cowpea mosaic virus nanoparticles target surface vimentin on cancer cells.

Nanomedicine (Lond). 2011-2

[5]
Optical nano-constructs composed of genome-depleted brome mosaic virus doped with a near infrared chromophore for potential biomedical applications.

ACS Nano. 2011-1-6

[6]
The art of engineering viral nanoparticles.

Mol Pharm. 2010-12-17

[7]
Intravital imaging of embryonic and tumor neovasculature using viral nanoparticles.

Nat Protoc. 2010-7-8

[8]
Hydrazone ligation strategy to assemble multifunctional viral nanoparticles for cell imaging and tumor targeting.

Nano Lett. 2010-3-10

[9]
Potato virus X as a novel platform for potential biomedical applications.

Nano Lett. 2010-1

[10]
Structure-based engineering of an icosahedral virus for nanomedicine and nanotechnology.

Curr Top Microbiol Immunol. 2009

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