Evaluation of Three Morphologically Distinct Virus-Like Particles as Nanocarriers for Convection-Enhanced Drug Delivery to Glioblastoma

Finbloom, Joel A.; Aanei, Ioana L.; Bernard, Jenna M.; Klass, Sarah H.; Elledge, Susanna K.; Han, Kenneth; Ozawa, Tomoko; Nicolaides, Theodore; Berger, Mitchel S.; Francis, Matthew

doi:10.3390/nano8121007

Evaluation of Three Morphologically Distinct Virus-Like Particles as Nanocarriers for Convection-Enhanced Drug Delivery to Glioblastoma

Journal Article · Wed Dec 05 00:00:00 EST 2018 · Nanomaterials

DOI:https://doi.org/10.3390/nano8121007· OSTI ID:1571946

Finbloom, Joel A. ^[1]; Aanei, Ioana L. ^[1]; Bernard, Jenna M. ^[1]; Klass, Sarah H. ^[1]; Elledge, Susanna K. ^[1]; Han, Kenneth ^[1]; Ozawa, Tomoko ^[2]; Nicolaides, Theodore ^[3]; Berger, Mitchel S. ^[2]; Francis, Matthew ^[4]

Univ. of California, Berkeley, CA (United States). Dept. of Chemistry
Univ. of California, San Francisco, CA (United States). Dept. of Neurological Surgery
NYU Langone Medical Center, New York, NY (United States). Dept. of Pediatrics
Univ. of California, Berkeley, CA (United States). Dept. of Chemistry; Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Materials Sciences Division

Glioblastoma is a particularly challenging cancer, as there are currently limited options for treatment. New delivery routes are being explored, including direct intratumoral injection via convection-enhanced delivery (CED). While promising, convection-enhanced delivery of traditional chemotherapeutics such as doxorubicin (DOX) has seen limited success. Several studies have demonstrated that attaching a drug to polymeric nanoscale materials can improve drug delivery efficacy via CED. We therefore set out to evaluate a panel of morphologically distinct protein nanoparticles for their potential as CED drug delivery vehicles for glioblastoma treatment. The panel consisted of three different virus-like particles (VLPs), MS2 spheres, tobacco mosaic virus (TMV) disks and nanophage filamentous rods modified with DOX. While all three VLPs displayed adequate drug delivery and cell uptake in vitro, increased survival rates were only observed for glioma-bearing mice that were treated via CED with TMV disks and MS2 spheres conjugated to doxorubicin, with TMV-treated mice showing the best response. Importantly, these improved survival rates were observed after only a single VLP–DOX CED injection several orders of magnitude smaller than traditional IV doses. Overall, this study underscores the potential of nanoscale chemotherapeutic CED using virus-like particles and illustrates the need for further studies into how the overall morphology of VLPs influences their drug delivery properties.

View Accepted Manuscript (DOE)

Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

Sponsoring Organization:: USDOE Office of Science (SC)

Grant/Contract Number:: AC02-05CH11231

OSTI ID:: 1571946

Journal Information:: Nanomaterials, Journal Name: Nanomaterials Journal Issue: 12 Vol. 8; ISSN 2079-4991; ISSN NANOKO

Publisher:: MDPICopyright Statement

Country of Publication:: United States

Language:: English

References (57)

Glioblastoma and Other Malignant Gliomas: A Clinical Review Omuro, Antonio JAMA, Vol. 310, Issue 17 https://doi.org/10.1001/jama.2013.280319	journal	November 2013
The Impact of Aspect Ratio on the Biodistribution and Tumor Homing of Rigid Soft-Matter Nanorods Shukla, Sourabh; Eber, Fabian J.; Nagarajan, Adithy S. Advanced Healthcare Materials, Vol. 4, Issue 6 https://doi.org/10.1002/adhm.201400641	journal	January 2015
Genome-Free Viral Capsids as Multivalent Carriers for Taxol Delivery Wu, Wesley; Hsiao, Sonny C.; Carrico, Zachary M. Angewandte Chemie International Edition, Vol. 48, Issue 50 https://doi.org/10.1002/anie.200902426	journal	November 2009
Enhancing Antibody Response against Small Molecular Hapten with Tobacco Mosaic Virus as a Polyvalent Carrier Zhao, Xia; Chen, Limin; Luckanagul, Jittima Amie ChemBioChem, Vol. 16, Issue 9 https://doi.org/10.1002/cbic.201500028	journal	May 2015
Convection-enhanced delivery of nanocarriers for the treatment of brain tumors Allard, Emilie; Passirani, Catherine; Benoit, Jean-Pierre Biomaterials, Vol. 30, Issue 12 https://doi.org/10.1016/j.biomaterials.2009.01.003	journal	April 2009
Effects of particle size and surface charge on cellular uptake and biodistribution of polymeric nanoparticles He, Chunbai; Hu, Yiping; Yin, Lichen Biomaterials, Vol. 31, Issue 13 https://doi.org/10.1016/j.biomaterials.2010.01.065	journal	May 2010
Polymeric anticancer drugs with pH-controlled activation Ulbrich, K.; Etrych, T.; Chytil, P. International Journal of Pharmaceutics, Vol. 277, Issue 1-2 https://doi.org/10.1016/j.ijpharm.2003.02.001	journal	June 2004
Transport of drugs across the blood–brain barrier by nanoparticles Wohlfart, Stefanie; Gelperina, Svetlana; Kreuter, Jörg Journal of Controlled Release, Vol. 161, Issue 2 https://doi.org/10.1016/j.jconrel.2011.08.017	journal	July 2012
Modeling the effects of vasculature evolution on early brain tumor growth Gevertz, Jana L.; Torquato, Salvatore Journal of Theoretical Biology, Vol. 243, Issue 4 https://doi.org/10.1016/j.jtbi.2006.07.002	journal	December 2006
Openings between Defective Endothelial Cells Explain Tumor Vessel Leakiness Hashizume, Hiroya; Baluk, Peter; Morikawa, Shunichi The American Journal of Pathology, Vol. 156, Issue 4 https://doi.org/10.1016/s0002-9440(10)65006-7	journal	April 2000
Stable Disk Assemblies of a Tobacco Mosaic Virus Mutant as Nanoscale Scaffolds for Applications in Drug Delivery Finbloom, Joel A.; Han, Kenneth; Aanei, Ioana L. Bioconjugate Chemistry, Vol. 27, Issue 10 https://doi.org/10.1021/acs.bioconjchem.6b00424	journal	September 2016
Biodistribution of Antibody-MS2 Viral Capsid Conjugates in Breast Cancer Models Aanei, Ioana L.; ElSohly, Adel M.; Farkas, Michelle E. Molecular Pharmaceutics, Vol. 13, Issue 11 https://doi.org/10.1021/acs.molpharmaceut.6b00566	journal	September 2016
Tobacco Mosaic Virus Delivery of Phenanthriplatin for Cancer therapy Czapar, Anna E.; Zheng, Yao-Rong; Riddell, Imogen A. ACS Nano, Vol. 10, Issue 4 https://doi.org/10.1021/acsnano.5b07360	journal	March 2016
Using Synthetically Modified Proteins to Make New Materials Witus, Leah S.; Francis, Matthew B. Accounts of Chemical Research, Vol. 44, Issue 9 https://doi.org/10.1021/ar2001292	journal	September 2011
Addition of sulfhydryl groups of Escherichia coli ribosomes by protein modification with 2-iminothiolane (methyl 4-mercaptobutyrimidate) Jue, Rodney; Lambert, John M.; Pierce, Leland R. Biochemistry, Vol. 17, Issue 25 https://doi.org/10.1021/bi00618a013	journal	December 1978
Glycan-Targeted Virus-like Nanoparticles for Photodynamic Therapy Rhee, Jin-Kyu; Baksh, Michael; Nycholat, Corwin Biomacromolecules, Vol. 13, Issue 8 https://doi.org/10.1021/bm300578p	journal	July 2012
Self-Assembling Light-Harvesting Systems from Synthetically Modified Tobacco Mosaic Virus Coat Proteins Miller, Rebekah A.; Presley, Andrew D.; Francis, Matthew B. Journal of the American Chemical Society, Vol. 129, Issue 11 https://doi.org/10.1021/ja063887t	journal	March 2007
P22 Viral Capsids as Nanocomposite High-Relaxivity MRI Contrast Agents Qazi, Shefah; Liepold, Lars O.; Abedin, Md Joynal Molecular Pharmaceutics, Vol. 10, Issue 1 https://doi.org/10.1021/mp300208g	journal	July 2012
Increased Tumor Homing and Tissue Penetration of the Filamentous Plant Viral Nanoparticle Potato virus X Shukla, Sourabh; Ablack, Amber L.; Wen, Amy M. Molecular Pharmaceutics, Vol. 10, Issue 1 https://doi.org/10.1021/mp300240m	journal	July 2012
PET Imaging and Biodistribution of Chemically Modified Bacteriophage MS2 Farkas, Michelle E.; Aanei, Ioana L.; Behrens, Christopher R. Molecular Pharmaceutics, Vol. 10, Issue 1 https://doi.org/10.1021/mp3003754	journal	November 2012
Determining the Size and Shape Dependence of Gold Nanoparticle Uptake into Mammalian Cells Chithrani, B. Devika; Ghazani, Arezou A.; Chan, Warren C. W. Nano Letters, Vol. 6, Issue 4 https://doi.org/10.1021/nl052396o	journal	April 2006
Host–guest encapsulation of materials by assembled virus protein cages Douglas, Trevor; Young, Mark Nature, Vol. 393, Issue 6681 https://doi.org/10.1038/30211	journal	May 1998
Gene therapy for human glioblastoma using neurotropic JC virus-like particles as a gene delivery vector Chao, Chun-Nun; Yang, Yu-Hsuan; Wu, Mu-Sheng Scientific Reports, Vol. 8, Issue 1 https://doi.org/10.1038/s41598-018-19825-w	journal	February 2018
New model of tumor angiogenesis: dynamic balance between vessel regression and growth mediated by angiopoietins and VEGF Holash, J.; Wiegand, S. J.; Yancopoulos, G. D. Oncogene, Vol. 18, Issue 38 https://doi.org/10.1038/sj.onc.1203035	journal	September 1999
A nanocarrier based on a genetically engineered protein cage to deliver doxorubicin to human hepatocellular carcinoma cells Toita, Riki; Murata, Masaharu; Abe, Kana Chemical Communications, Vol. 49, Issue 67 https://doi.org/10.1039/c3cc44508a	journal	January 2013
Design of virus-based nanomaterials for medicine, biotechnology, and energy Wen, Amy M.; Steinmetz, Nicole F. Chemical Society Reviews, Vol. 45, Issue 15 https://doi.org/10.1039/c5cs00287g	journal	January 2016
The effect of particle design on cellular internalization pathways Gratton, S. E. A.; Ropp, P. A.; Pohlhaus, P. D. Proceedings of the National Academy of Sciences, Vol. 105, Issue 33, p. 11613-11618 https://doi.org/10.1073/pnas.0801763105	journal	August 2008
Mammalian cells preferentially internalize hydrogel nanodiscs over nanorods and use shape-specific uptake mechanisms Agarwal, R.; Singh, V.; Jurney, P. Proceedings of the National Academy of Sciences, Vol. 110, Issue 43 https://doi.org/10.1073/pnas.1305000110	journal	October 2013
Quantitative Fluorescence Microscopy Measures Vascular Pore Size in Primary and Metastatic Brain Tumors Mittapalli, Rajendar K.; Adkins, Chris E.; Bohn, Kaci. A. Cancer Research, Vol. 77, Issue 2 https://doi.org/10.1158/0008-5472.can-16-1711	journal	November 2016
Multivalent Viral Capsids with Internal Cargo for Fibrin Imaging Obermeyer, Allie C.; Capehart, Stacy L.; Jarman, John B. PLoS ONE, Vol. 9, Issue 6 https://doi.org/10.1371/journal.pone.0100678	journal	June 2014
The blood-brain barrier: Bottleneck in brain drug development Pardridge, William M. NeuroRX, Vol. 2, Issue 1 https://doi.org/10.1602/neurorx.2.1.3	journal	January 2005
Pharmacokinetics of Pegylated Liposomal Doxorubicin: Review of Animal and Human Studies Gabizon, Alberto; Shmeeda, Hilary; Barenholz, Yechezkel Clinical Pharmacokinetics, Vol. 42, Issue 5 https://doi.org/10.2165/00003088-200342050-00002	journal	January 2003
Research Highlights: Highlights from the latest articles in nanomedicine Luby, Benjamin M.; Farhadi, Arash; Shakiba, Mojdeh Nanomedicine, Vol. 9, Issue 4 https://doi.org/10.2217/nnm.13.216	journal	March 2014
Establishing Intracranial Brain Tumor Xenografts With Subsequent Analysis of Tumor Growth and Response to Therapy using Bioluminescence Imaging Ozawa, Tomoko; James, C. David Journal of Visualized Experiments, Issue 41 https://doi.org/10.3791/1986-v	journal	July 2010
Why one-size-fits-all vaso-modulatory interventions fail to control glioma invasion: in silico insights Alfonso, J. C. L.; Kohn-Luque, A.; Stylianopoulos, T. arXiv https://doi.org/10.48550/arxiv.1604.05082	preprint	January 2016
Genome-Free Viral Capsids as Multivalent Carriers for Taxol Delivery Wu, Wesley; Hsiao, Sonny C.; Carrico, Zachary M. Angewandte Chemie, Vol. 121, Issue 50 https://doi.org/10.1002/ange.200902426	journal	November 2009
Cyclo(RGD)-Decorated Reduction-Responsive Nanogels Mediate Targeted Chemotherapy of Integrin Overexpressing Human Glioblastoma In Vivo Chen, Wei; Zou, Yan; Zhong, Zhiyuan Small, Vol. 13, Issue 6 https://doi.org/10.1002/smll.201601997	journal	November 2016
The blood-brain barrier: Bottleneck in brain drug development Pardridge, William M. Neurotherapeutics, Vol. 2, Issue 1 https://doi.org/10.1007/bf03206638	journal	January 2005
Openings between Defective Endothelial Cells Explain Tumor Vessel Leakiness Hashizume, Hiroya; Baluk, Peter; Morikawa, Shunichi The American Journal of Pathology, Vol. 156, Issue 4 https://doi.org/10.1016/S0002-9440(10)65006-7	journal	April 2000
The preferential targeting of the diseased microvasculature by disk-like particles Adriani, Giulia; de Tullio, Marco Donato; Ferrari, Mauro Biomaterials, Vol. 33, Issue 22 https://doi.org/10.1016/j.biomaterials.2012.04.027	journal	August 2012
Plant viruses and bacteriophages for drug delivery in medicine and biotechnology Czapar, Anna E.; Steinmetz, Nicole F. Current Opinion in Chemical Biology, Vol. 38 https://doi.org/10.1016/j.cbpa.2017.03.013	journal	June 2017
Functionalized nanogels carrying an anticancer microRNA for glioblastoma therapy Shatsberg, Zohar; Zhang, Xuejiao; Ofek, Paula Journal of Controlled Release, Vol. 239 https://doi.org/10.1016/j.jconrel.2016.08.029	journal	October 2016
Convection enhanced delivery of liposome encapsulated doxorubicin for brain tumour therapy Zhan, Wenbo; Wang, Chi-Hwa Journal of Controlled Release, Vol. 285 https://doi.org/10.1016/j.jconrel.2018.07.006	journal	September 2018
Convection-enhanced delivery of nanodiamond drug delivery platforms for intracranial tumor treatment Xi, Guifa; Robinson, Erik; Mania-Farnell, Barbara Nanomedicine: Nanotechnology, Biology and Medicine, Vol. 10, Issue 2 https://doi.org/10.1016/j.nano.2013.07.013	journal	February 2014
Diffusion and Uptake of Tobacco Mosaic Virus as Therapeutic Carrier in Tumor Tissue: Effect of Nanoparticle Aspect Ratio Chariou, Paul L.; Lee, Karin L.; Pokorski, Jonathan K. The Journal of Physical Chemistry B, Vol. 120, Issue 26 https://doi.org/10.1021/acs.jpcb.6b02163	journal	April 2016
Dual-Surface Modification of the Tobacco Mosaic Virus Schlick, Tara L.; Ding, Zhebo; Kovacs, Ernest W. Journal of the American Chemical Society, Vol. 127, Issue 11 https://doi.org/10.1021/ja046239n	journal	March 2005
N-Terminal Modification of Proteins with o -Aminophenols Obermeyer, Allie C.; Jarman, John B.; Francis, Matthew B. Journal of the American Chemical Society, Vol. 136, Issue 27 https://doi.org/10.1021/ja500728c	journal	June 2014
Nanoscale Protein Assemblies from a Circular Permutant of the Tobacco Mosaic Virus Dedeo, Michel T.; Duderstadt, Karl E.; Berger, James M. Nano Letters, Vol. 10, Issue 1 https://doi.org/10.1021/nl9032395	journal	January 2010
Nanoparticle-mediated cellular response is size-dependent Jiang, Wen; Kim, Betty Y. S.; Rutka, James T. Nature Nanotechnology, Vol. 3, Issue 3 https://doi.org/10.1038/nnano.2008.30	journal	March 2008
Why one-size-fits-all vaso-modulatory interventions fail to control glioma invasion: in silico insights Alfonso, J. C. L.; Köhn-Luque, A.; Stylianopoulos, T. Scientific Reports, Vol. 6, Issue 1 https://doi.org/10.1038/srep37283	journal	November 2016
Design of virus-based nanomaterials for medicine, biotechnology, and energy Wen, Amy M.; Steinmetz, Nicole F. Chemical Society Reviews, Vol. 45, Issue 15 https://doi.org/10.1039/C5CS00287G	journal	January 2016
Spherical Nucleic Acid Nanoparticle Conjugates as an RNAi-Based Therapy for Glioblastoma Jensen, S. A.; Day, E. S.; Ko, C. H. Science Translational Medicine, Vol. 5, Issue 209 https://doi.org/10.1126/scitranslmed.3006839	journal	October 2013
Quantitative Fluorescence Microscopy Measures Vascular Pore Size in Primary and Metastatic Brain Tumors Mittapalli, Rajendar K.; Adkins, Chris E.; Bohn, Kaci. A. Cancer Research, Vol. 77, Issue 2 https://doi.org/10.1158/0008-5472.CAN-16-1711	journal	November 2016
Convection-enhanced delivery of a topoisomerase I inhibitor (nanoliposomal topotecan) and a topoisomerase II inhibitor (pegylated liposomal doxorubicin) in intracranial brain tumor xenografts1 Yamashita, Yoji; Krauze, Michal T.; Kawaguchi, Tomohiro Neuro-Oncology, Vol. 9, Issue 1 https://doi.org/10.1215/15228517-2006-016	journal	January 2007
The effect of particle design on cellular internalization pathways J., Madden, V.; D., Pohlhaus, P.; M., DeSimone, J. The University of North Carolina at Chapel Hill University Libraries https://doi.org/10.17615/bf5g-4680	text	January 2008
Ff-nano, short functionalized nanorods derived from Ff (f1, fd, or M13) filamentous bacteriophage Sattar, Sadia; Bennett, Nicholas J.; Wen, Wesley X. Frontiers in Microbiology, Vol. 6 https://doi.org/10.3389/fmicb.2015.00316	journal	April 2015
Establishing Intracranial Brain Tumor Xenografts With Subsequent Analysis of Tumor Growth and Response to Therapy using Bioluminescence Imaging Ozawa, Tomoko; James, C. David Journal of Visualized Experiments, Issue 41 https://doi.org/10.3791/1986	journal	January 2010

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Evaluation of Three Morphologically Distinct Virus-Like Particles as Nanocarriers for Convection-Enhanced Drug Delivery to Glioblastoma

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