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Ultrasound-mediated oncolytic virus delivery and uptake for increased therapeutic efficacy: state of art

Authors Nande R, Howard C, Claudio PP

Received 15 June 2015

Accepted for publication 23 September 2015

Published 25 November 2015 Volume 2015:4 Pages 193—205

DOI https://doi.org/10.2147/OV.S66097

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Ahmed Al-Shammari

Peer reviewer comments 3

Editor who approved publication: Dr Faris Farassati

Rounak Nande,1 Candace M Howard,2 Pier Paolo Claudio,3,4

1Department of Biochemistry and Microbiology, Marshall University School of Medicine, Huntington, WV, 2Department of Radiology, University of Mississippi Medical Center, Jackson, MS, 3Department of BioMolecular Sciences and National Center for Natural Products Research, School of Pharmacy, University of Mississippi, MS, 4Department of Radiation Oncology, University of Mississippi Medical Center, Jackson, MS, USA


Abstract: The field of ultrasound (US) has changed significantly from medical imaging and diagnosis to treatment strategies. US contrast agents or microbubbles (MB) are currently being used as potential carriers for chemodrugs, small molecules, nucleic acids, small interfering ribonucleic acid, proteins, adenoviruses, and oncolytic viruses. Oncolytic viruses can selectively replicate within and destroy a cancer cell, thus making them a powerful therapeutic in treating late-stage or metastatic cancer. These viruses have been shown to have robust activity in clinical trials when injected directly into tumor nodules. However limitations in oncolytic virus’ effectiveness and its delivery approach have warranted exploration of ultrasound-mediated delivery. Gene therapy bearing adenoviruses or oncolytic viruses can be coupled with MBs and injected intravenously. Following application of US energy to the target region, the MBs cavitate, and the resulting shock wave enhances drug, gene, or adenovirus uptake. Though the underlying mechanism is yet to be fully understood, there is evidence to suggest that mechanical pore formation of cellular membranes allows for the temporary uptake of drugs. This delivery method circumvents the limitations due to stimulation of the immune system that prevented intravenous administration of viruses. This review provides insight into this intriguing new frontier on the delivery of oncolytic viruses to tumor sites.

Keywords: microbubbles, ultrasound, ultrasound-contrast agent, oncolytic virus, adenovirus, gene therapy

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