Devising Biocompatible, NIR-Activated Helical Pyroptosis Agents via ��-Twisting Strategy for Promoting Antitumor...

Area of Science:

• Biomedical Engineering
• Photodynamic Therapy
• Cancer Immunotherapy

Background:

• Controlling pyroptosis offers a dual approach for cancer treatment, enabling tumor destruction and immune system activation.
• Developing efficient and safe pyroptosis inducers is crucial for effective oncotherapy.

Purpose of the Study:

• To design and synthesize novel near-infrared (NIR)-activated helical pyroptosis agents (PyroAs).
• To evaluate the efficacy of these PyroAs in triggering pyroptosis, ablating tumors, and stimulating anti-tumor immunity in vivo.

Main Methods:

• Constructed helical BODIPY (^HBD) molecules with intramolecular B-X bonds to enhance photosensitivity.
• Extended ^HBD absorption into the NIR region via ester moiety incorporation.
• Engineered NIR-activated ^HBD-ER for targeted endoplasmic reticulum (ER) delivery to activate pyroptosis.

Main Results:

• Synthesized helical ^HBD molecules exhibited high photosensitivity and low dark toxicity.
• NIR-activated ^HBD-ER specifically induced pyroptosis via ER targeting.
• Demonstrated favorable biocompatibility, potent anti-tumor efficacy, and significant immune response in vivo.

Conclusions:

• The developed NIR-activated helical PyroAs show significant potential for solid tumor immunotherapy.
• This strategy offers a promising approach for simultaneous tumor ablation and immune activation.