Ferroptosis Induction by Fenbendazole Combined With Photothermal Therapy Triggers Dual-Immunotherapy Against Bladder...

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Cancer Therapy

Background:

• Bladder cancer presents high incidence and recurrence rates, necessitating novel therapeutic strategies.
• Ferroptosis, a form of regulated cell death, is a promising avenue for cancer treatment.
• Current treatments often lack specificity and can lead to significant side effects.

Purpose of the Study:

• To develop and evaluate a novel intravesical nanoplatform, FBZ@BSA@PDA, for synergistic bladder cancer treatment.
• To investigate the combined effects of ferroptosis, immunogenic cell death (ICD), and photothermal therapy (PTT).
• To assess the platform's efficacy and biosafety in an orthotopic mouse model.

Main Methods:

• Fabrication of FBZ@BSA@PDA nanoplatform encapsulating fenbendazole (FBZ) with polydopamine (PDA) coating.
• Intravesical administration in an orthotopic mouse model of bladder cancer.
• Evaluation of ferroptosis induction (LPO, GSH depletion), ICD markers (CRT, HMGB1, ATP), immune cell activation, and anti-tumor efficacy.
• Assessment of localized PTT and sustained drug release.

Main Results:

• FBZ@BSA@PDA demonstrated sustained drug release and effective localized PTT.
• The nanoplatform successfully induced ferroptosis through lipid peroxidation and mitochondrial dysfunction.
• Key ICD markers were upregulated, promoting dendritic cell maturation and T-cell activation.
• Significant anti-tumor efficacy and favorable biosafety were observed in vivo.

Conclusions:

• The FBZ@BSA@PDA nanoplatform offers a promising synergistic therapeutic strategy for bladder cancer.
• The integrated approach of ferroptosis, ICD, and PTT enhances anti-tumor response.
• This localized, immune-potentiated treatment modality holds potential for clinical translation.