Piezoelectric-Triggered Ferroptosis for Cancer Therapy via Cascade-Enhanced Immune Response

Area of Science:

• Biomedical Engineering
• Materials Science
• Immunology

Background:

• Ferroptosis, a form of programmed cell death, shows promise in cancer therapy due to its ability to release damage-associated molecular patterns (DAMPs) and activate immune responses.
• The immunogenicity of ferroptosis and methods for controllably activating self-enhanced antitumor immunity require further research.

Purpose of the Study:

• To synthesize a piezoelectric material, BTO@Fe, for ferroptosis induction and cancer immunotherapy.
• To investigate the combined effects of ultrasound (US) irradiation and BTO@Fe on ferroptosis and antitumor immune responses.

Main Methods:

• Synthesis of a piezoelectric BaTiO3-based ferroptosis inducer (BTO@Fe).
• Induction of ferroptosis via iron and Fenton reaction catalysis, enhanced by ultrasound-induced piezocatalysis.
• Evaluation of reactive oxygen species (ROS) generation, glutathione (GSH) consumption, and immunogenic cell death (ICD).
• Assessment of CD8+ T cell activation, interferon gamma (IFNγ) release, and in vitro/in vivo antitumor efficacy.

Main Results:

• BTO@Fe effectively induces moderate ferroptosis, amplified by ultrasound.
• Ultrasound-activated BTO@Fe enhances ROS generation and GSH consumption, leading to intensified ferroptosis and ICD.
• The treatment stimulated CD8+ T cell responses and IFNγ release, sensitizing tumor cells to ferroptosis.
• Significant in vitro and in vivo antitumor effects were observed.

Conclusions:

• Engineered piezoelectric materials with enhanced catalytic activity can restore immunogenicity in ferroptotic cells.
• BTO@Fe combined with ultrasound presents a promising strategy for cancer immunotherapy by leveraging ferroptosis and immune activation.