An Acid-Responsive Iron-Based Nanocomposite for OSCC Treatment

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Oncology

Background:

• Oral squamous cell carcinoma (OSCC) presents significant treatment challenges due to its invasiveness and metastatic potential.
• The tumor microenvironment's unique characteristics, such as mild acidity and high H2O2 levels, offer therapeutic opportunities.
• Targeted therapies for OSCC remain limited, necessitating innovative treatment approaches.

Purpose of the Study:

• To develop an acid-responsive iron-based nanocomposite for targeted OSCC treatment.
• To investigate the efficacy of the developed nanocomposite in inhibiting OSCC proliferation, invasion, and metastasis.
• To elucidate the underlying mechanisms of OSCC cell death induced by the nanocomposite.

Main Methods:

• Loading ultra-small Prussian blue nanoparticles (USPBNPs) into mesoporous calcium-silicate nanoparticles (MCSNs) to create USPBNPs@MCSNs (UPM).
• Evaluating UPM's dual enzyme activities in acidic and neutral environments.
• Assessing UPM's impact on OSCC cell proliferation, migration, invasion, and in vivo tumor growth in mice.
• Analyzing the molecular mechanisms, including ferroptosis induction via the xCT/GPX4/glutathione (GSH) axis.

Main Results:

• UPM demonstrated excellent dual enzyme activities, generating toxic hydroxyl radicals (·OH) in acidic conditions and oxygen (O2) in neutral conditions.
• UPM effectively inhibited OSCC cell proliferation, migration, invasion, and reduced tumor growth in mice with minimal systemic toxicity.
• UPM was found to induce ferroptosis in OSCC cells by downregulating the xCT/GPX4/glutathione (GSH) axis, leading to characteristic cellular changes.

Conclusions:

• USPBNPs@MCSNs (UPM) is a promising nano-composite for oral squamous cell carcinoma treatment.
• UPM effectively targets OSCC by inducing ferroptosis, offering a novel therapeutic avenue.
• This research provides strong evidence for ferroptosis as a viable therapeutic target for OSCC.