Ultrasound Dual-Driven Curcumin-Enriched Turmeric Microemulsion For OSCC Treatment

Oral squamous cell carcinoma (OSCC) is the most common malignant tumor in the head and neck region. Although sonodynamic therapy (SDT) with ultrasound shows promise as a treatment approach, existing sonosensitizers frequently present challenges including toxic side effects and complicated preparation processes. This study presents a safer, more accessible alternative by introducing a novel, naturally-derived therapeutic agent. We report the first extraction of curcumin-enriched microemulsion (CM) from turmeric, which significantly improve curcumin's solubility and bioavailability. These microemulsion were modified with cRGD peptides through click chemistry, creating microemulsion-peptide conjugates (CMC) that can target tumor blood vessels. Due to its high curcumin solubility and enhanced absorption by endothelial cells, CMC exhibited excellent sonodynamic performance and significantly inhibited the migration and tube formation ability of endothelial cells. Under low-frequency ultrasound, CMC reduce to nano-size, allowing better uptake by tumor cells and enhancing curcumin's ability to promote tumor Cell apoptosis. In OSCC mouse models, CMC effectively target tumors and, when combined with ultrasound, significantly disrupt tumor blood vessels and induce tumor cell death. This study develops a natural, curcumin-rich emulsion that works through dual sonodynamic mechanisms, offering a new approach for OSCC treatment. It maximizes the therapeutic potential of curcumin as both a natural sonosensitizer and anti-tumor agent, providing a promising strategy for treating oral squamous cell carcinoma with reduced side effects and improved efficacy compared to conventional methods