MicroRNA-based therapies for ovarian cancer enhanced by ultrasound-targeted microbubble destruction: Mechanistic basis, preclinical evidence, and translational challenges

Background Ovarian cancer remains a lethal gynecologic malignancy because of late presentation, recurrence, and treatment resistance. MicroRNA (miRNA)-based therapeutics can modulate multiple oncogenic pathways, but clinical development is constrained by nuclease degradation, non-specific biodistribution, immune and off-target effects, and inefficient delivery to tumor tissue. Ultrasound-targeted microbubble destruction (UTMD) is being investigated as a spatially controlled delivery approach that uses microbubble cavitation to transiently increase vascular and cellular permeability. Methods We conducted a structured narrative review of the mechanistic, preclinical, and translational literature on UTMD- and ultrasound-assisted delivery strategies relevant to ovarian cancer, with emphasis on miRNA delivery, cavitation/sonoporation, carrier design, cancer stem-cell models, drug-resistance pathways, safety, and barriers to clinical translation. The literature-identification approach and search strings are reported for transparency; this article is not presented as a PRISMA systematic review or meta-analysis. Results Evidence for UTMD-facilitated miRNA therapy in ovarian cancer is predominantly preclinical. Individual cell and xenograft studies report increased local nucleic-acid uptake, target-gene modulation, apoptosis, and tumor-growth suppression when ultrasound is combined with microbubble- or nanobubble-based carriers. However, effect estimates are study-specific, experimental platforms and acoustic parameters are heterogeneous, and no pooled effect size or clinical efficacy estimate is available. Standard microbubbles are primarily intravascular and have circulation half-lives measured in minutes; their therapeutic effect depends on ultrasound-induced vascular permeabilization and payload transfer rather than reliable microbubble extravasation. Evidence for cancer-stem-cell targeting, chemotherapy combinations, and hypoxia modulation remains experimental, and formal pharmacological synergy has rarely been demonstrated. Conclusion UTMD is a technically plausible strategy for improving local delivery of miRNA and other therapeutics, but its role in ovarian cancer remains investigational. Translation requires reproducible acoustic dosimetry, standardized microbubble dosing and cavitation monitoring, characterization of the injection-to-sonication window, validation in orthotopic and patient-relevant models, and careful evaluation of vascular injury, immune toxicity, and miRNA off-target effects. No UTMD-miRNA regimen has established clinical efficacy in ovarian cancer.