Combination Therapeutic Effect of Asiatic Acid & Curcumin-Loaded Liposomes Modified by Neutrophil Extracellular Traps for the Treatment of Oral Squamous Cell Carcinoma.

BACKGROUND

Tumor metastasis has been proven to represent the predominant cause of cancer-related mortality; therefore, the strategies simultaneously eradicating primary lesions and blocking dissemination cascades hold revolutionary potential in curative oral squamous cell carcinoma (OSCC) therapy.

METHODS

In this study, we designed novel neutrophil extracellular traps (NETs)-coating liposomes (CUR@AA-NLIP) for co-delivery of curcumin (CUR) and asiatic acid (AA), in which the introduction of NETs was expected to improve tumor-targeting ability, and the combination of CUR and AA was used to synergistically inhibit tumor development.

RESULTS

The characteristics analysis showed that CUR@AA-NLIP exhibited uniform size, phospholipid bilayer structure, and sustained drug release. In vitro studies demonstrated that CUR@AA-NLIP enhanced tumor cell uptake and macrophage escape, inhibited fibroblast activation and vessel tube formation, showing enhanced anti-proliferation and anti-migration capacities. In vivo results confirmed that CUR@AA-NLIP increased drug accumulation in the tumor region, showed enhanced anti-tumor efficacy (> 80% tumor suppression), and reduced lung metastasis.

CONCLUSION

CUR@AA-NLIP holds great potentials in OSCC-targeting delivery of synergistic natural compounds and can achieve anti-proliferative and anti-metastatic effects by simultaneously enhancing tumor accumulation, reducing immune system clearance, and inhibiting of cancer-associated fibroblast (CAF) activation and angiogenesis, therefore exhibiting enhanced anti-OSCC efficacy.