Assembling Ruthenium Complexes to Form Ruthenosome Unleashing Ferritinophagy-Mediated Tumor Suppression

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Cancer Therapy

Background:

• Metallodrugs offer unique therapeutic avenues in cancer treatment.
• Ferroptosis, a regulated cell death pathway, presents a promising target for cancer therapy.
• Developing novel drug delivery systems is crucial for enhancing therapeutic efficacy.

Purpose of the Study:

• To introduce ruthenosomes, a novel class of ferroptosis inducers (FINs).
• To engineer ruthenium complexes into liposome-like nanocarriers for cancer therapy.
• To investigate the mechanism of action and therapeutic potential of ruthenosomes.

Main Methods:

• Self-assembly of oleate-conjugated ruthenium complexes into ruthenosomes.
• Assessment of cellular uptake and mitochondrial accumulation.
• Evaluation of reactive oxygen species (ROS) generation, autophagy, and ferritinophagy induction.
• In vivo studies on colorectal tumor growth suppression.

Main Results:

• Ruthenosomes demonstrated high cellular uptake and selective mitochondrial accumulation.
• Targeted mitochondrial disruption led to elevated ROS levels, triggering autophagy and ferritinophagy.
• These events sensitized cancer cells to ferroptosis.
• Ruthenosomes effectively suppressed colorectal tumor growth in vivo.

Conclusions:

• Ruthenosomes are potent, light-independent ferroptosis inducers.
• This study presents a novel design strategy for metallodrugs as multifunctional nanocarriers.
• Ruthenosomes offer a promising platform for ROS-mediated, ferroptosis-driven cancer cell eradication.