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Improved Tumor Control Following Radiosensitization with Ultrasound-Sensitive Oxygen Microbubbles and Tumor Mitochondrial Respiration Inhibitors in a Preclinical Model of Head and Neck Cancer
Journal article   Open access   Peer reviewed

Improved Tumor Control Following Radiosensitization with Ultrasound-Sensitive Oxygen Microbubbles and Tumor Mitochondrial Respiration Inhibitors in a Preclinical Model of Head and Neck Cancer

Quezia Lacerda, Hebah Falatah, Ji-Bin Liu, Corinne E Wessner, Brian Oeffinger, Ankit Rochani, Dennis B Leeper, Flemming Forsberg, Joseph M Curry, Gagan Kaushal, …
Pharmaceutics, v 15(4), 1302
21 Apr 2023
DOI: https://doi.org/10.3390/pharmaceutics15041302
PMID: 37111787
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://doi.org/10.3390/pharmaceutics15041302View
Published, Version of Record (VoR)CC BY V4.0,  Open

Abstract

head and neck cancer contrast-enhanced ultrasound lonidamine tumor hypoxia metformin drug delivery oxygen-loaded microbubbles Radiotherapy
Tumor hypoxia (oxygen deficiency) is a major contributor to radiotherapy resistance. Ultrasound-sensitive microbubbles containing oxygen have been explored as a mechanism for overcoming tumor hypoxia locally prior to radiotherapy. Previously, our group demonstrated the ability to encapsulate and deliver a pharmacological inhibitor of tumor mitochondrial respiration (lonidamine (LND)), which resulted in ultrasound-sensitive microbubbles loaded with O and LND providing prolonged oxygenation relative to oxygenated microbubbles alone. This follow-up study aimed to evaluate the therapeutic response to radiation following the administration of oxygen microbubbles combined with tumor mitochondrial respiration inhibitors in a head and neck squamous cell carcinoma (HNSCC) tumor model. The influences of different radiation dose rates and treatment combinations were also explored. The results demonstrated that the co-delivery of O and LND successfully sensitized HNSCC tumors to radiation, and this was also enhanced with oral metformin, significantly slowing tumor growth relative to unsensitized controls (< 0.01). Microbubble sensitization was also shown to improve overall animal survival. Importantly, effects were found to be radiation dose-rate-dependent, reflecting the transient nature of tumor oxygenation.

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15 citations in Web of Science
11 citations in Scopus

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Web of Science research areas
Pharmacology & Pharmacy
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