Engineering ruthenium(II)-based nanoparticles for synergistic sonodynamic therapy with multi-targeted redox catalysis

Area of Science:

• Materials Science
• Nanotechnology
• Biomedical Engineering

Background:

• Sonodynamic therapy (SDT) offers advantages over photodynamic therapy (PDT) by overcoming light limitations.
• Current sonosensitizer design prioritizes acceptor engineering, often compromising biocompatibility.
• A donor-engineering approach is proposed to improve sonosensitizer performance and safety.

Purpose of the Study:

• To develop a novel donor-engineered sonosensitizer for enhanced cancer therapy.
• To create tumor-targeted nanoparticles for improved drug delivery and efficacy.
• To investigate the therapeutic effects and mechanisms of the developed nanoplatform in colorectal cancer.

Main Methods:

• Synthesized a series of Ruthenium(II) complexes ([Ru(tpy)(Aze-phen)Cl](PF6)) utilizing a donor-engineering strategy.
• Formulated tumor-targeted nanoparticles (NanoRu) via self-assembly with DSPE-PEG2000.
• Evaluated NanoRu's efficacy in vitro and in vivo using cancer cell lines and CT26 tumor models under ultrasound irradiation.

Main Results:

• The donor-engineered complex demonstrated significantly higher NADH sonocatalytic oxidation efficiency compared to analogues.
• NanoRu nanoparticles effectively targeted mitochondria and cell nuclei, inducing synergistic therapeutic effects.
• Significant tumor regression (83%) was observed in mice, alongside evidence of ferroptosis, apoptosis, and DNA damage.

Conclusions:

• The developed Ru(II)-based platform represents a breakthrough in sonosensitizer design through donor engineering.
• NanoRu nanoparticles show promise for overcoming chemoresistance and advancing precision sonodynamic-chemotherapy.
• This approach offers a new strategy for developing effective and biocompatible sonosensitizers for cancer treatment.