Manganese-Based Redox Homeostasis Disruptor for Inducing Intense Ferroptosis/Apoptosis Through xCT Inhibition And...

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Cancer Research

Background:

• Intracellular redox homeostasis is crucial for tumor progression and treatment resistance.
• Targeting redox balance impairment presents a promising strategy for cancer therapy.

Purpose of the Study:

• To develop a manganese-based homeostasis modulator (MHS) for cancer treatment.
• To investigate the mechanisms of MHS in inducing cancer cell death via ferroptosis and apoptosis.

Main Methods:

• Development of a manganese-based homeostasis modulator (MHS) nanocarrier.
• Investigating MHS-induced reactive oxygen species accumulation and glutathione depletion.
• Evaluating MHS efficacy in sonodynamic therapy, chemodynamic therapy, and combination therapy with sulfasalazine.
• Assessing MHS-induced ferroptosis and apoptosis in vitro and in vivo.

Main Results:

• MHS induces severe reactive oxygen species accumulation and glutathione deprivation, leading to ferroptosis and apoptosis.
• Tumor-specific degradation of MHS alleviates hypoxia and releases cargo, enhancing apoptosis via synergistic therapies.
• MHS inhibits cystine antiporter xCT, suppressing glutathione biosynthesis and promoting ferroptosis.
• MHS demonstrates significant antitumor effects in vitro and in vivo, eliciting antitumor immunity.

Conclusions:

• MHS is an effective strategy for inducing ferroptosis and apoptosis in cancer.
• Manganese-derived nanoagents show potential for expanded medical applications in cancer therapeutics.