A pyroptosis proportion tunable nano-modulator for cancer immunotherapy

Area of Science:

• Biomedical Engineering
• Cancer Research
• Immunotherapy

Background:

• Pyroptosis, a programmed cell death pathway mediated by gasdermin proteins, shows promise in cancer immunotherapy.
• Precise control over pyroptosis induction in cancer cells is crucial to mitigate biosafety concerns and systemic toxicity.

Purpose of the Study:

• To develop a tumor-targeted and tunable pyroptosis-inducing strategy for enhanced antitumor efficacy.
• To minimize systemic side effects associated with pyroptosis induction in cancer therapy.

Main Methods:

• Designed an H2S-activated nanomodulator with an optical switch for tumor-specific pyroptosis induction.
• Utilized synergistic effects of photothermal temperature modulation and demethylation to trigger Gasdermin-E-mediated pyroptosis.
• Precisely controlled the proportion of pyroptosis induction within a tunable range (0-31%) in colorectal cancer cells.

Main Results:

• Successfully induced tunable pyroptosis in microsatellite-stable colorectal cancer cells.
• Demonstrated enhanced antitumor efficacy with minimized systemic side effects.
• Validated the safety and effectiveness of photothermal modulation and demethylation for controlled pyroptosis.

Conclusions:

• Presents a novel and precise method for controlling pyroptosis using photothermal temperature modulation.
• Provides guidance for in vivo applications of pyroptosis-inducing nanomedicines.
• Offers insights into developing safe and effective cancer therapies with adjustable pyroptosis induction.