Titanium Dioxide Nanoparticles Trigger Non-Canonical Receptor Endocytosis to Inhibit Wnt Signaling.

Area of Science:

• Nanotechnology
• Cellular Biology
• Toxicology

Background:

• Biocompatible nanoparticles (NPs) show promise in biomedical applications.
• Long-term health effects of nanomaterials are not well understood.
• Titanium dioxide nanoparticles (TiO₂NPs) are widely used.

Purpose of the Study:

• To investigate the effects of TiO₂NPs on Wnt signaling.
• To elucidate the molecular mechanisms underlying TiO₂NP-Wnt pathway interactions.
• To assess potential risks and benefits of TiO₂NP applications.

Main Methods:

• Utilized in vitro and in vivo models.
• Examined TiO₂NPs (10 nm and 50 nm) effects on Wnt signaling.
• Investigated Wnt receptor Lrp6 trafficking and beta-catenin nuclear entry.

Main Results:

• TiO₂NPs inhibited Wnt signaling at non-cytotoxic concentrations.
• Observed reduced cancer cell metastasis, impaired adipocyte differentiation, and defective Zebrafish development.
• Demonstrated TiO₂NPs induce non-canonical endocytic trafficking of Lrp6, reducing beta-catenin nuclear entry.

Conclusions:

• TiO₂NPs interfere with Wnt signaling by altering Lrp6 trafficking.
• Findings reveal potential risks and benefits of TiO₂NPs in biological systems.
• Highlights the interaction between synthetic NPs and cellular signaling pathways.