Local Delivery of miR-27a* Using Ultrasound-Targeted Microbubble Cavitation Inhibits Squamous Cell Carcinoma Growth.

Area of Science:

• Biomedical Engineering
• Molecular Oncology
• Drug Delivery Systems

Background:

• Ultrasound-targeted microbubble cavitation (UTMC) is an image-guided platform for delivering therapeutic oligonucleotides.
• Microbubbles (MBs) carry payloads on their shells and facilitate cellular uptake via ultrasound-induced oscillation, bypassing endocytosis.
• This technology targets specific tissues for enhanced therapeutic delivery.

Purpose of the Study:

• To evaluate the efficacy of UTMC-mediated delivery of miR-27a* in reducing tumor growth rate.
• To determine if UTMC enhances miR-27a* accumulation within tumor cells and the tumor microenvironment.
• To assess the impact of miR-27a* delivery on key protein targets in head and neck squamous cell carcinoma models.

Main Methods:

• UTMC was employed to deliver miR-27a* to SCC-VII cells in vitro and in SCC-VII mouse tumor models.
• Pulsed ultrasound was applied during intravenous infusion of lipid-encapsulated microbubbles loaded with either miR-27a* or a negative control.
• Treatment groups included miR-27a*-MB + UTMC, Con-miR-MB + UTMC, intravenous miR-27a*, and no treatment.

Main Results:

• miR-27a*-MB + UTMC significantly reduced SCC-VII cell viability in vitro and tumor growth in vivo compared to controls.
• Protein expression of miR-27a* targets (EGFR, NUP62, ΔNP63α) was significantly decreased by miR-27a*-MB + UTMC.
• UTMC delivery resulted in a 50%-75% reduction in tumor expression of EGFR, NUP62, and ΔNP63α compared to non-treated tumors.

Conclusions:

• UTMC is effective for non-invasive delivery of oligonucleotide payloads to extravascular sites.
• miR-27a* delivered via UTMC demonstrates significant therapeutic potential for head and neck squamous cell carcinoma.
• This approach offers a promising strategy for targeted cancer therapy.