Sono-responsive hybrid amorphous TiO2/polymer nanoparticles for targeted sonodynamic therapy of pediatric cancer

Safe and effective targeting of anticancer treatment to diseased tissue is one of the crucial challenges in cancer therapy, with many approaches developed so far. Sonodynamic therapy (SDT) is an evolved version of photodynamic therapy, while instead of reactive oxygen species (ROS) production under UV-Vis, the sono-responsive agent becomes cytotoxic under ultrasound (US) irradiation. SDT has several advantages: deep tissue penetration, lower off-target effect, and lower tissue heating. Most SDT strategies involve the use of liposomes filled with high amounts of sonosensitizers, with the spatial release of encapsulated molecules over time. Moreover, fine control of the nanoparticle size is crucial to optimize its accumulation in the target tissue. We developed a new family of hybrid nanomaterials, made of amorphous titanium dioxide (TiO2) and amphiphilic block copolymers that exhibit several integrated features – (i) active targeting and enhanced accumulation in solid tumors, (ii) responsiveness to the US, and (iii) drug-loading capability. These nanomaterials are synthesized by a simple, reproducible, and scalable method that relies on the formation of a Ti(IV) oxo-organo complex, it`s mixing with the polymeric component and their nanoprecipitation in water. Owing to the modularity of the nanoparticle composition, the nanoparticle surface can be modified with glucose derivatives to actively target solid tumors that overexpress glucose transporters. Moreover, the size of the nanoparticles can be tailored between tens to hundreds of nanometers by changing the aging time of the oxo-organo complex. Nanoparticles have shown good compatibility in pediatric cancer cells in vitro and upon US-activation, they produce ROS and trigger cell apoptosis. The next steps will investigate the performance of these novel sono-responsive nanoparticles in murine models of pediatric tumors.