Augmenting Cancer Therapy with a Supramolecular Immunogenic Cell Death Inducer: A Lysosome-Targeted...

Area of Science:

• Supramolecular Chemistry
• Materials Science
• Immunotherapy

Background:

• Immunogenic cell death (ICD) is crucial for anticancer therapies.
• Stimulating robust immune responses in deep-seated tumors with minimal side effects remains a significant challenge.

Purpose of the Study:

• To introduce a novel self-assembled near-infrared-light-activated ruthenium(II) metallacycle, Ru1105, as a supramolecular ICD inducer.
• To evaluate its efficacy in potentiating immunomodulatory responses and reducing adverse effects in deep-seated tumors.

Main Methods:

• Development of a Ru(II) supramolecular metallacycle (Ru1105) activated by near-infrared (NIR) light.
• Assessment of ROS generation, tumor penetration, cellular uptake, and ICD induction in vitro and in vivo.
• Comparison with oxaliplatin for ICD efficacy and dose-response.

Main Results:

• Ru1105 demonstrated depth-activated ROS production (~1 cm) with resistance to diffusion and anti-ROS quenching.
• Effective cellular uptake and ROS generation in cancer cells and multicellular tumor spheroids.
• Ru1105 induced more efficient ICD at an ultralow dose (10 μM) compared to oxaliplatin (300 μM).
• In vivo studies showed Ru1105 elicited CD8+ T cell responses and depleted Foxp3+ T cells with minimal adverse effects.

Conclusions:

• Ru1105 is the first Ru(II) supramolecular ICD inducer, synergistically enhancing immunomodulatory responses.
• It offers a potent and secure metal-based strategy for immunotherapy against deep-seated tumors.