Near-Infrared Light-Responsive Immunomodulator Prodrugs Rejuvenating Immune Microenvironment for "Cold" Tumor...

Area of Science:

• Biomedical Engineering
• Photodynamic Therapy
• Cancer Immunotherapy

Background:

• Light-activatable prodrugs offer spatiotemporal control for cancer therapy.
• Current systems limited to UV/visible light restrict deep tissue applications.
• Developing near-infrared (NIR) activatable systems is crucial for advanced cancer treatment.

Purpose of the Study:

• To develop novel 808 nm light-activatable prodrugs for "cold" tumor photoimmunotherapy.
• To create a NIR-activated controlled release system for imiquimod (R837) using a reactive oxygen species (ROS)-cleavable linker.
• To investigate the combined efficacy of R837 immunotherapy and phototherapy against tumor metastasis.

Main Methods:

• Conjugation of imiquimod (R837) with a NIR boron dipyrromethene (BODIPY) dye via an ROS-cleavable linker.
• Activation of the prodrug using 808 nm laser irradiation to generate ROS and cleave the linker.
• Evaluation of drug release, immune response, immunogenic cell death, and antitumor effects in preclinical models.

Main Results:

• The BODIPY-based prodrug successfully released R837 spatiotemporally upon 808 nm laser irradiation.
• The combination therapy significantly enhanced adaptive antitumor immunity.
• Increased cytotoxic CD8+ T cell infiltration was observed, leading to suppressed tumor metastasis and inhibited distant tumor growth.

Conclusions:

• This work presents an effective NIR light-activatable controlled release system for cancer immunotherapy.
• The developed system shows promise for suppressing tumor metastasis and treating "cold" tumors.
• This approach offers a new strategy for precision cancer therapy with minimal side effects.