Hybrid Amorphous Titanium Dioxide/Amphiphilic Graft Copolymer Nano-Sonosensitizers

Sonodynamic therapy (SDT) is an innovative anticancer strategy that combines a sonosensitizer with low-intensity ultrasound (US) to selectively kill cancer cells. Sonosensitizers can be classified into organic small-molecules, and inorganic and hybrid nanomaterials. In this work, we investigate the synthesis, the morphology, the nanostructure and, the sono-responsiveness of hybrid nanomaterials that combine amorphous titanium dioxide with an amphiphilic poly(vinyl alcohol)-graft-poly(methyl methacrylate) copolymer. The process comprises the synthesis of a Ti (IV) oxo-organo complex in dry acetone and its aging, its combination with the amphiphilic graft copolymer in a dimethyl sulfoxide/acetone co-solvent mixture and, a nanoprecipitation step in aqueous medium of variable pH. Upon optimization of the synthetic methology, nanoparticles with sizes in the 100-200 nm range, as measured by dynamic light scattering, and irregular morphology as visualized by different electron microscopies, are produced. Energy dispersive X-ray spectroscopy analysis confirms the homogenous integration of both the ceramic and the polymeric components in the nanoparticle nanostructure. Finally, we preliminarily assess the sonodynamic activity of these hybrid nanoparticles in the rhabdomyosarcoma cell line Rh30 in vitro. Results show a statistically significant decrease in cancer cell viability upon exposure to these sono-responsive nanoparticles and US (frequency of 1 MHz, intensity of 1.2 W/cm2 for 3 min) and highlight the promise of this flexible synthetic pathway to produce hybrid nano-sonosensitizers with a variety of sizes and morphologies.