A novel combination of hydroxyl-enriched fullerenol and mTOR inhibitors reveals regulatory mechanisms of organelle communication networks in preclinical models, establishing a synergistic “nanomaterial + metabolic modulation” anticancer strategy.

Breakthrough Cancer Strategy Hijacks Tumor Cells’ Survival Network

Researchers have developed a nanoparticle-based therapy that disrupts cancer cells’ organelle communication system – the hidden network allowing tumors to resist conventional treatments. By combining multi-hydroxyl fullerene (MF) nanoparticles with mTOR inhibitors, this approach triggers the domino-like collapse of lysosomes (“cellular recycling centers”), mitochondria (“power plants”), and endoplasmic reticulum (“protein factories”) while sabotaging cancer cells’ self-repair mechanisms.

Key Innovations:

Organelle-Targeted Strike

MF nanoparticles selectively rupture lysosome membranes, releasing digestive enzymes that disable mitochondria and trigger endoplasmic reticulum stress. Concurrent mTOR inhibitor treatment first activates and then blocks autophagy, leaving cancer cells unable to clear damaged components.

Self-Destruction Switch

The therapy intentionally activates autophagy (cells’ cleanup system) but disables its completion through lysosome destruction. This “traps” cancer cells in a lethal cycle of damage accumulation.

Safety by Design

Normal cells exhibited a 3.7-fold greater survival rate compared to cancer cells at the IC50 concentration, as they maintain more robust organelle networks. Tumors shrank by 60.4% without detectable organ toxicity.

Significance:

This work pioneers a “physical biology” anticancer paradigm using nanomaterials to disrupt cellular infrastructure rather than targeting genes/proteins. It offers new hope for treating aggressive cancers resistant to existing therapies.

Original Source: https://www.sciencedirect.com/science/article/pii/S2095927325002002

Expert Contact
Chunru Wang
Institute of Chemistry, Chinese Academy of Sciences
crwang@iccas.ac.cn

Original Publication
Hedong Qi, Xue Li, Jing Ma, Jiacheng Sun, Yating Liu, Xin Wang, Kelong Fan, Chunying Shu, Chunru Wang
Journal: Science Bulletin
Method of Research: Experimental study
Article Title: Fullerenols hijack lysosomes to disrupt inter-organellar crosstalk and block autophagy pre-activated by mTOR inhibitors for cancer cell PANoptosis
Article Publication Date: 25 February 2025
DOI: 10.1016/j.scib.2025.02.034

Media Contact
Bei Yan
Science China Press
yanbei@scichina.com

Source: EurekAlert!