Optical Nano-Constructs Composed of Genome-Depleted <i>Brome Mosaic Virus </i>Doped with a Near Infrared Chromophore for Potential Biomedical Applications

Jung, Bongsu; Rao, A. L. N.; Anvari, Bahman

doi:10.1021/nn1028696

Cited by 60 publications

(81 citation statements)

References 79 publications

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“…Similarly, the CP of a closely related virus, brome mosaic virus (BMV), has been shown to package gold nanoparticles of various sizes that have been functionalized with anionic moieties (43) and a negatively charged near-infrared chromophore (26). Also, we have investigated the packaging by CCMV CP of poly(styrene sulfonate) (PSS) polymers with molecular masses ranging from 38 kDa to 3.4 MDa (12,23).…”

mentioning

confidence: 99%

Self-Assembly of Viral Capsid Protein and RNA Molecules of Different Sizes: Requirement for a Specific High Protein/RNA Mass Ratio

Cadena-Nava

Comas-García

Garmann

et al. 2012

J Virol

164

222

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Virus-like particles can be formed by self-assembly of capsid protein (CP) with RNA molecules of increasing length. If the protein "insisted" on a single radius of curvature, the capsids would be identical in size, independent of RNA length. However, there would be a limit to length of the RNA, and one would not expect RNA much shorter than native viral RNA to be packaged unless multiple copies were packaged. On the other hand, if the protein did not favor predetermined capsid size, one would expect the capsid diameter to increase with increase in RNA length. Here we examine the self-assembly of CP from cowpea chlorotic mottle virus with RNA molecules ranging in length from 140 to 12,000 nucleotides (nt). Each of these RNAs is completely packaged if and only if the protein/RNA mass ratio is sufficiently high; this critical value is the same for all of the RNAs and corresponds to equal RNA and N-terminal-protein charges in the assembly mix. For RNAs much shorter in length than the 3,000 nt of the viral RNA, two or more molecules are assembled into 24-and 26-nm-diameter capsids, whereas for much longer RNAs (>4,500 nt), a single RNA molecule is shared/packaged by two or more capsids with diameters as large as 30 nm. For intermediate lengths, a single RNA is assembled into 26-nm-diameter capsids, the size associated with T‫3؍‬ wild-type virus. The significance of these assembly results is discussed in relation to likely factors that maintain T‫3؍‬ symmetry in vivo.

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mentioning

confidence: 99%

Self-Assembly of Viral Capsid Protein and RNA Molecules of Different Sizes: Requirement for a Specific High Protein/RNA Mass Ratio

Cadena-Nava

Comas-García

Garmann

et al. 2012

J Virol

164

222

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“…Alexa Fluor 647) and polyethylene glycol (PEG). The dyes facilitate tracking and detection of the VNPs [5][6][7][8][9][10] , and PEG reduces immunogenicity of the proteinaceous nanoparticles while enhancing their pharmacokinetics 8,11 . We demonstrate tumor homing of PEGylated VNPs using a mouse xenograft tumor model.…”

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confidence: 99%

Viral Nanoparticles for <em>In vivo</em> Tumor Imaging

Wen

Lee

Yildiz

et al. 2012

JoVE

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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 3. The structure of VNPs is known to atomic resolution, and modifications can be carried out with spatial precision at the atomic level 4 , 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 [5][6][7][8][9][10] , and PEG reduces immunogenicity of the proteinaceous nanoparticles while enhancing their pharmacokinetics 8,11 . 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 12 . 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. Video LinkThe video component of this article can be found at

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“…We isolate BMV and purify the capsid protein using previously established methods [1]. By making use of BMV capsid protein's natural tendency to self-assemble at low pH and high ionic concentrations, we encapsulate ICG within the reassembled capsid protein shell.…”

Section: Ovg Fabricationmentioning

confidence: 99%

“…Our nanoparticle formulation provides a new approach which has proven to effectively target and selectively label ovarian cancer cells with high-HER-2 expression levels. Our OVGs are composed of plant-infecting genome-depleted BMV capsid protein encapsulating ICG [1], and surface-functionalized with monoclonal anti-HER-2 antibody. This technology may provide enhanced contrast essential for tumor removal during cytoreductive surgery.…”

Section: Introductionmentioning

confidence: 99%

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Targeted imaging of ovarian cancer cells using viral nanoparticles doped with indocyanine green

et al. 2013

Self Cite

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Our group has constructed a new type of viral nanoparticles (VNPs) from genome-depleted plant infecting brome mosaic virus (BMV) that encapsulates the FDA-approved near infrared (NIR) indocyanine green (ICG) [1]. We refer to these VNPs as optical viral ghosts (OVGs) since the constructs lack the genomic content of wild-type BMV. One of our areas of interest is the application of OVGs for real-time intraoperative NIR fluorescence imaging of small peritoneal ovarian tumor nodules. We target human epidermal growth factor receptor-2 (HER-2) expression in ovarian cancer as a biomarker associated with ovarian cancer, since its over-expression is linked to the disease's progression to death. We functionalize the OVGs with anti-HER-2 monoclonal antibodies using reductive amination methods. We used fluorescence imaging to visualize the SKOV-3 cells (high HER-2 expression) after incubation with free ICG, OVGs, and functionalized OVGs. Our results suggest the possibility of using anti-HER2 conjugated OVGs in conjunction with cytoreductive surgery to detect small tumor nodules (<5cm) which currently are not excised during surgery.

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Optical Nano-Constructs Composed of Genome-Depleted Brome Mosaic Virus Doped with a Near Infrared Chromophore for Potential Biomedical Applications

Cited by 60 publications

References 79 publications

Self-Assembly of Viral Capsid Protein and RNA Molecules of Different Sizes: Requirement for a Specific High Protein/RNA Mass Ratio

Self-Assembly of Viral Capsid Protein and RNA Molecules of Different Sizes: Requirement for a Specific High Protein/RNA Mass Ratio

Viral Nanoparticles for <em>In vivo</em> Tumor Imaging

Targeted imaging of ovarian cancer cells using viral nanoparticles doped with indocyanine green

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