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Title: Viruslike Nanoparticles with Maghemite Cores Allow for Enhanced MRI Contrast Agents

Abstract

Here, for the first time, we demonstrate formation of virus-like nanoparticles (VNPs) utilizing gold-coated iron oxide nanoparticles as cores and capsidprotein of brome mosaic virus (BMV) or hepatitis B virus (HBV) as shells. Further, utilizing cryo-electron microscopy and single particle methods, we are able to show that the BMV coat on VNPs assembles into a structure very close to that of a native virion. This is a consequence of an optimal iron oxide NP size (~11 nm) fitting the virus cavity and an ultrathin gold layer on the maghemite cores, which allows for utilization of SH-(CH2)11-(CH2-CH2-O)4-OCH2-COOH as capping molecules to provide sufficient stability, charge density, and small form factor. MRI studies show unique relaxivity ratios that diminish only slightly with gold coating. In conclusion, a virus protein coating of a magnetic core mimicking the wild-type virus makes these VNPs a versatile platform for biomedical applications.

Authors:
 [1];  [1];  [1];  [2];  [3];  [1];  [4];  [1];  [2];  [1];  [5]
  1. Department of Chemistry, Indiana University, 800 East Kirkwood Avenue, Bloomington, Indiana 47405, United States
  2. European Molecular Biology Laboratory (EMBL), Hamburg Outstation, Notkestraße 85, D-22603 Hamburg, Germany
  3. Department of Psychological and Brain Sciences, Indiana University, 1101 East Tenth Street, Bloomington, Indiana 47403, United States
  4. Department of Biology, Indiana University, 1001 East Third Street, Bloomington, Indiana 47405, United States
  5. Department of Chemistry, Indiana University, 800 East Kirkwood Avenue, Bloomington, Indiana 47405, United States, Department of Physics, Faculty of Science , King Abdulaziz University, Jeddah, Saudi Arabia
Publication Date:
Research Org.:
Indiana Univ., Bloomington, IN (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Basic Energy Sciences (BES)
OSTI Identifier:
1167524
Alternate Identifier(s):
OSTI ID: 1440972
Grant/Contract Number:  
SC0010507
Resource Type:
Published Article
Journal Name:
Chemistry of Materials
Additional Journal Information:
Journal Name: Chemistry of Materials Journal Volume: 27 Journal Issue: 1; Journal ID: ISSN 0897-4756
Publisher:
American Chemical Society
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES

Citation Formats

Malyutin, Andrey G., Easterday, Rosemary, Lozovyy, Yaroslav, Spilotros, Alessandro, Cheng, Hu, Sanchez-Felix, Olivia R., Stein, Barry D., Morgan, David Gene, Svergun, Dmitri I., Dragnea, Bogdan, and Bronstein, Lyudmila M. Viruslike Nanoparticles with Maghemite Cores Allow for Enhanced MRI Contrast Agents. United States: N. p., 2014. Web. doi:10.1021/cm504029j.
Malyutin, Andrey G., Easterday, Rosemary, Lozovyy, Yaroslav, Spilotros, Alessandro, Cheng, Hu, Sanchez-Felix, Olivia R., Stein, Barry D., Morgan, David Gene, Svergun, Dmitri I., Dragnea, Bogdan, & Bronstein, Lyudmila M. Viruslike Nanoparticles with Maghemite Cores Allow for Enhanced MRI Contrast Agents. United States. https://doi.org/10.1021/cm504029j
Malyutin, Andrey G., Easterday, Rosemary, Lozovyy, Yaroslav, Spilotros, Alessandro, Cheng, Hu, Sanchez-Felix, Olivia R., Stein, Barry D., Morgan, David Gene, Svergun, Dmitri I., Dragnea, Bogdan, and Bronstein, Lyudmila M. Tue . "Viruslike Nanoparticles with Maghemite Cores Allow for Enhanced MRI Contrast Agents". United States. https://doi.org/10.1021/cm504029j.
@article{osti_1167524,
title = {Viruslike Nanoparticles with Maghemite Cores Allow for Enhanced MRI Contrast Agents},
author = {Malyutin, Andrey G. and Easterday, Rosemary and Lozovyy, Yaroslav and Spilotros, Alessandro and Cheng, Hu and Sanchez-Felix, Olivia R. and Stein, Barry D. and Morgan, David Gene and Svergun, Dmitri I. and Dragnea, Bogdan and Bronstein, Lyudmila M.},
abstractNote = {Here, for the first time, we demonstrate formation of virus-like nanoparticles (VNPs) utilizing gold-coated iron oxide nanoparticles as cores and capsidprotein of brome mosaic virus (BMV) or hepatitis B virus (HBV) as shells. Further, utilizing cryo-electron microscopy and single particle methods, we are able to show that the BMV coat on VNPs assembles into a structure very close to that of a native virion. This is a consequence of an optimal iron oxide NP size (~11 nm) fitting the virus cavity and an ultrathin gold layer on the maghemite cores, which allows for utilization of SH-(CH2)11-(CH2-CH2-O)4-OCH2-COOH as capping molecules to provide sufficient stability, charge density, and small form factor. MRI studies show unique relaxivity ratios that diminish only slightly with gold coating. In conclusion, a virus protein coating of a magnetic core mimicking the wild-type virus makes these VNPs a versatile platform for biomedical applications.},
doi = {10.1021/cm504029j},
journal = {Chemistry of Materials},
number = 1,
volume = 27,
place = {United States},
year = {2014},
month = {12}
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record
https://doi.org/10.1021/cm504029j

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Cited by: 15 works
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Works referenced in this record:

Versatile Three-Dimensional Virus-Based Template for Dye-Sensitized Solar Cells with Improved Electron Transport and Light Harvesting
journal, July 2013

  • Chen, Po-Yen; Dang, Xiangnan; Klug, Matthew T.
  • ACS Nano, Vol. 7, Issue 8
  • DOI: 10.1021/nn4014164

Influence of Iron Oleate Complex Structure on Iron Oxide Nanoparticle Formation
journal, July 2007

  • Bronstein, Lyudmila M.; Huang, Xinlei; Retrum, John
  • Chemistry of Materials, Vol. 19, Issue 15
  • DOI: 10.1021/cm062948j

Relaxivities of hydrogen protons in aqueous solutions of gold-coated manganese ferrite nanoparticles
journal, June 2013

  • Ahmad, Tanveer; Iqbal, Yousaf; Bae, Hongsub
  • Journal of the Korean Physical Society, Vol. 62, Issue 11
  • DOI: 10.3938/jkps.62.1696

Gold-Coated Iron Oxide Glyconanoparticles for MRI, CT, and US Multimodal Imaging
journal, October 2013

  • Carril, Mónica; Fernández, Itziar; Rodríguez, Juan
  • Particle & Particle Systems Characterization, Vol. 31, Issue 1
  • DOI: 10.1002/ppsc.201300239

Hepatitis Virus Capsid Polymorph Stability Depends on Encapsulated Cargo Size
journal, September 2013

  • He, Li; Porterfield, Zachary; van der Schoot, Paul
  • ACS Nano, Vol. 7, Issue 10
  • DOI: 10.1021/nn4017839

Determination of the regularization parameter in indirect-transform methods using perceptual criteria
journal, August 1992


Viruses: Making Friends with Old Foes
journal, May 2006


Gene Delivery Using Herpes Simplex Virus Vectors
journal, December 2002


Viruses and protein cages as nanocontainers and nanoreactors
journal, January 2009

  • de la Escosura, Andrés; Nolte, Roeland J. M.; Cornelissen, Jeroen J. L. M.
  • Journal of Materials Chemistry, Vol. 19, Issue 16
  • DOI: 10.1039/b815274h

PRIMUS: a Windows PC-based system for small-angle scattering data analysis
journal, September 2003

  • Konarev, Petr V.; Volkov, Vladimir V.; Sokolova, Anna V.
  • Journal of Applied Crystallography, Vol. 36, Issue 5, p. 1277-1282
  • DOI: 10.1107/S0021889803012779

Magnetic Core/Shell Fe 3 O 4 /Au and Fe 3 O 4 /Au/Ag Nanoparticles with Tunable Plasmonic Properties
journal, July 2007

  • Xu, Zhichuan; Hou, Yanglong; Sun, Shouheng
  • Journal of the American Chemical Society, Vol. 129, Issue 28
  • DOI: 10.1021/ja073057v

Viral nanoparticles as tools for intravital vascular imaging
journal, February 2006

  • Lewis, John D.; Destito, Giuseppe; Zijlstra, Andries
  • Nature Medicine, Vol. 12, Issue 3
  • DOI: 10.1038/nm1368

Full-Length Hepatitis B Virus Core Protein Packages Viral and Heterologous RNA with Similarly High Levels of Cooperativity
journal, April 2010

  • Porterfield, J. Z.; Dhason, M. S.; Loeb, D. D.
  • Journal of Virology, Vol. 84, Issue 14
  • DOI: 10.1128/JVI.00586-10

Controlled Synthesis and Chemical Conversions of FeO Nanoparticles
journal, July 2007

  • Hou, Yanglong; Xu, Zhichuan; Sun, Shouheng
  • Angewandte Chemie International Edition, Vol. 46, Issue 33
  • DOI: 10.1002/anie.200701694

Quantum Dot Encapsulation in Viral Capsids
journal, September 2006

  • Dixit, Suraj K.; Goicochea, Nancy L.; Daniel, Marie-Christine
  • Nano Letters, Vol. 6, Issue 9
  • DOI: 10.1021/nl061165u

Applying Molecular Crowding Models to Simulations of Virus Capsid Assembly In Vitro
journal, January 2014


Gold-coated iron nanoparticles for biomedical applications
journal, May 2003

  • Chen, Min; Yamamuro, Saeki; Farrell, Dorothy
  • Journal of Applied Physics, Vol. 93, Issue 10
  • DOI: 10.1063/1.1555312

AUTO3DEM—an automated and high throughput program for image reconstruction of icosahedral particles
journal, January 2007

  • Yan, Xiaodong; Sinkovits, Robert S.; Baker, Timothy S.
  • Journal of Structural Biology, Vol. 157, Issue 1
  • DOI: 10.1016/j.jsb.2006.08.007

Self-Assembled Virus-like Particles with Magnetic Cores
journal, August 2007

  • Huang, Xinlei; Bronstein, Lyudmila M.; Retrum, John
  • Nano Letters, Vol. 7, Issue 8
  • DOI: 10.1021/nl071083l

Structure and Properties of Iron Oxide Nanoparticles Encapsulated by Phospholipids with Poly(ethylene glycol) Tails
journal, December 2007

  • Shtykova, Eleonora V.; Huang, Xinlei; Remmes, Nicholas
  • The Journal of Physical Chemistry C, Vol. 111, Issue 49
  • DOI: 10.1021/jp075235c

Medical application of functionalized magnetic nanoparticles
journal, July 2005

  • Ito, Akira; Shinkai, Masashige; Honda, Hiroyuki
  • Journal of Bioscience and Bioengineering, Vol. 100, Issue 1
  • DOI: 10.1263/jbb.100.1

Granting specificity for breast cancer cells using a hepatitis B core particle with a HER2-targeted affibody molecule
journal, December 2012

  • Nishimura, Y.; Mimura, W.; Mohamed Suffian, I. F.
  • Journal of Biochemistry, Vol. 153, Issue 3
  • DOI: 10.1093/jb/mvs140

Nanoparticle-Templated Assembly of Viral Protein Cages
journal, April 2006

  • Chen, Chao; Daniel, Marie-Christine; Quinkert, Zachary T.
  • Nano Letters, Vol. 6, Issue 4
  • DOI: 10.1021/nl0600878

Inorganic Nanoparticles for MRI Contrast Agents
journal, June 2009

  • Na, Hyon Bin; Song, In Chan; Hyeon, Taeghwan
  • Advanced Materials, Vol. 21, Issue 21, p. 2133-2148
  • DOI: 10.1002/adma.200802366

Hydrophobic Nanocrystals Coated with an Amphiphilic Polymer Shell:  A General Route to Water Soluble Nanocrystals
journal, April 2004

  • Pellegrino, Teresa; Manna, Liberato; Kudera, Stefan
  • Nano Letters, Vol. 4, Issue 4, p. 703-707
  • DOI: 10.1021/nl035172j

Role of Surface Charge Density in Nanoparticle-Templated Assembly of Bromovirus Protein Cages
journal, June 2010

  • Daniel, Marie-Christine; Tsvetkova, Irina B.; Quinkert, Zachary T.
  • ACS Nano, Vol. 4, Issue 7
  • DOI: 10.1021/nn1005073

Host–guest encapsulation of materials by assembled virus protein cages
journal, May 1998

  • Douglas, Trevor; Young, Mark
  • Nature, Vol. 393, Issue 6681
  • DOI: 10.1038/30211

Synthesis of Fe Oxide Core/Au Shell Nanoparticles by Iterative Hydroxylamine Seeding
journal, April 2004

  • Lyon, Jennifer L.; Fleming, David A.; Stone, Matthew B.
  • Nano Letters, Vol. 4, Issue 4, p. 719-723
  • DOI: 10.1021/nl035253f

Self-Assembly of Virus-Structured High Surface Area Nanomaterials and Their Application as Battery Electrodes
journal, February 2008

  • Royston, Elizabeth; Ghosh, Ayan; Kofinas, Peter
  • Langmuir, Vol. 24, Issue 3
  • DOI: 10.1021/la7016424

Water-soluble magnetic glyconanoparticles based on metal-doped ferrites coated with gold: Synthesis and characterization
journal, January 2010

  • Gallo, Juan; García, Isabel; Padro, Daniel
  • Journal of Materials Chemistry, Vol. 20, Issue 44
  • DOI: 10.1039/c0jm01756f

EMAN2: An extensible image processing suite for electron microscopy
journal, January 2007

  • Tang, Guang; Peng, Liwei; Baldwin, Philip R.
  • Journal of Structural Biology, Vol. 157, Issue 1
  • DOI: 10.1016/j.jsb.2006.05.009

Control of Protein Structure and Function through Surface Recognition by Tailored Nanoparticle Scaffolds
journal, January 2004

  • Hong, Rui; Fischer, Nicholas O.; Verma, Ayush
  • Journal of the American Chemical Society, Vol. 126, Issue 3
  • DOI: 10.1021/ja037470o

Hydrophilic Monodisperse Magnetic Nanoparticles Protected by an Amphiphilic Alternating Copolymer
journal, October 2008

  • Shtykova, Eleonora V.; Huang, Xinlei; Gao, Xinfeng
  • The Journal of Physical Chemistry C, Vol. 112, Issue 43
  • DOI: 10.1021/jp8053636

A Bayesian View on Cryo-EM Structure Determination
journal, January 2012


Cisplatin drug delivery using gold-coated iron oxide nanoparticles for enhanced tumour targeting with external magnetic fields
journal, December 2012


RELION: Implementation of a Bayesian approach to cryo-EM structure determination
journal, December 2012


From The Cover: Origin of icosahedral symmetry in viruses
journal, October 2004

  • Zandi, R.; Reguera, D.; Bruinsma, R. F.
  • Proceedings of the National Academy of Sciences, Vol. 101, Issue 44
  • DOI: 10.1073/pnas.0405844101

Pathway switching in templated virus-like particle assembly
journal, January 2012

  • Tsvetkova, Irina; Chen, Chao; Rana, Subinoy
  • Soft Matter, Vol. 8, Issue 17
  • DOI: 10.1039/c2sm00024e

Viral nanoparticles as platforms for next-generation therapeutics and imaging devices
journal, October 2010


Development of Cowpea Mosaic Virus as a High-Yielding System for the Presentation of Foreign Peptides
journal, August 1994


AAV does the shuffle
journal, February 2006

  • Asokan, Aravind; Samulski, R. Jude
  • Nature Biotechnology, Vol. 24, Issue 2
  • DOI: 10.1038/nbt0206-158

Chemical modification of a viral cage for multivalent presentation
journal, September 2002

  • Gillitzer, Eric; Willits, Debbie; Young, Mark
  • Chemical Communications, Issue 20
  • DOI: 10.1039/b207853h

Core-controlled polymorphism in virus-like particles
journal, January 2007

  • Sun, J.; DuFort, C.; Daniel, M. -C.
  • Proceedings of the National Academy of Sciences, Vol. 104, Issue 4
  • DOI: 10.1073/pnas.0610542104

Ultrasmall superparamagnetic iron oxide: characterization of a new class of contrast agents for MR imaging.
journal, May 1990


Two to Tango: Regulation of Mammalian Iron Metabolism
journal, July 2010


Electrostatic assembly of binary nanoparticle superlattices using protein cages
journal, December 2012

  • Kostiainen, Mauri A.; Hiekkataipale, Panu; Laiho, Ari
  • Nature Nanotechnology, Vol. 8, Issue 1
  • DOI: 10.1038/nnano.2012.220