Faculty, Staff and Student Publications

Language

English

Publication Date

2-1-2026

Journal

Ultrasound in Medicine and Biology

DOI

10.1016/j.ultrasmedbio.2025.10.018

PMID

41274844

Abstract

Objective: Ultrasound-targeted microbubble (MB) cavitation (UTMC) is an image-guided therapeutic oligonucleotide delivery platform utilizing intravenously injected gas-filled ultrasound contrast agents, which carry the therapeutic on the MB shell. During transit of MBs in the microcirculation of target tissue, ultrasound causes MB oscillation, facilitating endocytosis-independent payload uptake within insonified cells. Here, we tested the hypothesis that UTMC-mediated miR-27a* delivery will reduce tumor growth rate and result in accumulation of miR-27a* within tumor cells and the tumor microenvironment.

Methods: We used UTMC to deliver miR-27a* to SCC-VII cells in vitro and in SCC-VII mouse tumor models. Pulsed ultrasound was delivered during intravenous (i.v.) infusion of lipid encapsulated MBs loading either miR-27a* (miR-27a*-MB + UTMC) or negative control MBs (Con-miR-MB + UTMC).

Results: miR-27a*-MB+UTMC treatment significantly reduced SCC-VII cell viability in vitro and SCC-VII tumor growth in vivo compared to negative controls (Con-miR-MB+UTMC, i.v. miR-27a* or no treatment). Forty-eight hours following treatment, protein expression of direct miR-27a* targets (epidermal growth factor receptor [EGFR], NUP62 and ΔNP63α) was significantly reduced in miR-27a*-MB + UTMC vs i.v. miR-27a* or Con-miR-MB + UTMC. Further, whereas i.v. miR-27a* did not decrease tumor expression of these proteins vs. non-treated tumors, miR-27a*-MB + UTMC significantly reduced tumor expression of EGFR, NUP62 and ΔNP63α by 50%-75%, compared to non-treated tumors.

Conclusion: These data substantiate the utility of UTMC for non-invasive delivery of oligonucleotide payloads to extravascular target sites and suggests the therapeutic potential of miR-27a* for the treatment of head and neck squamous cell carcinoma.

Keywords

Animals, MicroRNAs, Microbubbles, Mice, Carcinoma, Squamous Cell, Cell Line, Tumor, Disease Models, Animal, Gene and drug delivery, Squamous cell carcinoma, Ultrasound-targeted microbubble cavitation, miR-27a*

Published Open-Access

yes

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