MF-094 nanodelivery inhibits oral squamous cell carcinoma by targeting USP30

Background: Oral squamous cell carcinoma (OSCC) is a common head and neck cancer, and the incidence of OSCC is increasing. As the mortality of OSCC keeps increasing, it is crucial to clarify its pathogenesis and develop new therapeutic strategies. Methods: Confocal laser scanning microscopy was used to evaluate the uptake of nanoparticles (NPs). The potential functions of USP30 were evaluated by cell counting kit (CCK)-8, flow cytometry, biochemical assay, coimmunoprecipitation, qRT-PCR, and immunoblotting. The antitumor effect of NP-loaded USP30 inhibitor MF-094 was evaluated in vitro and in vivo. Results: In this study, increased USP30 expression was found in OSCC specimens and cell lines through qRT-PCR and immunoblotting. CCK-8, flow cytometry, and biochemical assay revealed that the deubiquitylated catalytic activity of USP30 contributed to cell viability and glutamine consumption of OSCC. Subsequently, USP30 inhibitor MF-094 was loaded in ZIF-8-PDA and PEGTK to fabricate ZIF-8-PDA-PEGTK nanoparticles, which exhibited excellent inhibition of cell viability and glutamine consumption of OSCC, both in vitro and in vivo. Conclusion: The results indicated the clinical significance of USP30 and showed that nanocomposites provide a targeted drug delivery system for treating OSCC.

Automated summary

This study revealed the overexpression of USP30 in OSCC and demonstrated its role in cell viability and glutamine consumption through deubiquitylation activity. The utilization of USP30 inhibitor MF-094 loaded in nanoparticles effectively inhibited cell viability and glutamine consumption of OSCC, providing a novel strategy for treating OSCC.