Solubilization of a Hydrophobic Prodrug and the Ultrasound Irradiation Effect to TiO₂ Nanoparticles-Incorporated Polyion Complex Micelles

Abstract

Sonodynamic therapy (SDT) using ultrasound irradiation instead of photoactivation as in photodynamic therapy, has emerged as a promising treatment for various types of cancer. We have focused on titanium dioxide nanoparticles (TiO₂ NPs) as a sonosensitizer which can generate reactive oxygen species by sonication. TiO₂ NPs-incorporated polyion complex micelles were developed for the delivery into the cells. Here, carmofur being a hydrophobic prodrug was solubilized into the micelles. From in vitro experiments, it was confirmed that carmofur-solubilized micelles effectively suppress the cell viability due to the additive effect of the anticancer effect of 5-fluorouracil produced by hydrolysis of carmofur and the SDT effect.