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

1
Department of Chemistry, University of California, Berkeley, CA 94720, USA
2
Department of Neurological Surgery, University of California, San Francisco, CA 94158, USA
3
Department of Pediatrics, NYU Langone Medical Center, New York, NY 10016, USA
4
Materials Sciences Division, Lawrence Berkeley National Laboratories, Berkeley, CA 94720, USA
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Nanomaterials 2018, 8(12), 1007; https://doi.org/10.3390/nano8121007
Received: 13 November 2018 / Revised: 30 November 2018 / Accepted: 1 December 2018 / Published: 5 December 2018
(This article belongs to the Special Issue Virus-Based Nanomaterials and Nanostructures)
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Abstract

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 Full-Text
Keywords: virus-like particles; glioblastoma; convection-enhanced delivery; tobacco mosaic virus; bioconjugation; doxorubicin; drug delivery; protein-based nanomaterials; viral capsid virus-like particles; glioblastoma; convection-enhanced delivery; tobacco mosaic virus; bioconjugation; doxorubicin; drug delivery; protein-based nanomaterials; viral capsid
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Finbloom, J.A.; Aanei, I.L.; Bernard, J.M.; Klass, S.H.; Elledge, S.K.; Han, K.; Ozawa, T.; Nicolaides, T.P.; Berger, M.S.; Francis, M.B. Evaluation of Three Morphologically Distinct Virus-Like Particles as Nanocarriers for Convection-Enhanced Drug Delivery to Glioblastoma. Nanomaterials 2018, 8, 1007.

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