A novel extracellular vesicle (EV)-based nanodrug for tongue squamous cell carcinoma: in vitro efficacy in HNO-97 cells

Squamous cell carcinoma of the tongue (TSCC) is an aggressive malignancy with few therapeutic modalities available. Cisplatin, a commonly used chemotherapeutic drug, is often associated with significant toxicities and resistance. The use of an exosome-enriched fraction of extracellular vesicles (EVs) as a drug delivery system has become an attractive way to potentiate therapeutic effects and decrease toxicity. In particular, our focus is to study the therapeutic effect of cisplatin-loaded EVs obtained from umbilical cord mesenchymal stem cells (UC-MSCs) on TSCC. The goal is to assess the functionality of cancer cells and to characterize the EVs loaded with cisplatin. Cisplatin was incorporated into EVs derived from UC-MSCs. Characterization was performed using transmission electron microscopy (TEM) for morphology, BCA assay for protein quantification, and HPLC for drug loading efficiency. The presence of apoptotic bodies was evaluated using cytotoxicity assays and inverted phase-contrast microscopy to assess the effects of EV-encapsulated cisplatin on TSCC cells. Cisplatin-encapsulated EVs presented a statistically significantly more cytotoxic effect on cancer cells than unencapsulated cisplatin, with the half-maximal inhibitory concentration (IC50) of the EV formulation (1.64 µg/mL) representing a 25% enhancement in potency compared to free cisplatin (2.18 µg/mL; p < 0.05). Conclusion: UC-MSCs-derived EVs represent a promising strategy for a more localized and effective cisplatin delivery with potential improvement in TSCC chemotherapy efficacy while minimizing conventional chemotherapy-related side effects.