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MF-094 nanodelivery inhibits oral squamous cell carcinoma by targeting USP30
Xinyu Zhang1,2,3, Yong Han1,2,3, Shuli Liu1,2,3
1Department of Oral and Maxillofacial-Head and Neck Oncology, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, No.639 Zhizaoju Road, Huangpu District, Shanghai, 200011, China.
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.
Insights
Oral squamous cell carcinoma (OSCC) is a growing cancer. Targeting USP30 with novel nanoparticles (NPs) shows promise for inhibiting cancer cell growth and glutamine consumption, offering new therapeutic strategies.
Area of Science:
- Oncology
- Nanotechnology
- Biochemistry
Background:
- Oral squamous cell carcinoma (OSCC) is a prevalent and increasing head and neck cancer with rising mortality rates.
- Understanding OSCC pathogenesis is critical for developing effective therapeutic interventions.
Purpose of the Study:
- To investigate the role of USP30 in OSCC pathogenesis.
- To evaluate the therapeutic potential of a USP30 inhibitor loaded into nanoparticles for OSCC treatment.
Main Methods:
- USP30 expression was analyzed in OSCC tissues and cell lines using qRT-PCR and immunoblotting.
- Cell viability and glutamine consumption were assessed using CCK-8, flow cytometry, and biochemical assays.
- Nanoparticles (ZIF-8-PDA-PEGTK) loaded with USP30 inhibitor MF-094 were fabricated and evaluated in vitro and in vivo.
Main Results:
- USP30 expression is upregulated in OSCC, correlating with increased cell viability and glutamine consumption.
- The USP30 inhibitor MF-094 demonstrated significant inhibition of OSCC cell viability and glutamine consumption.
- Fabricated nanoparticles effectively delivered MF-094, showing potent antitumor effects in vitro and in vivo.
Conclusions:
- USP30 plays a significant role in OSCC progression and represents a potential therapeutic target.
- Nanocomposite drug delivery systems offer a targeted approach for OSCC treatment.
