We have investigated polyion complex (PIC) micelles incorporating TiO2 nanoparticles (NPs) in the core for sonodynamic therapy (SDT). TiO2 NPs-incorporated PIC micelles were prepared by mixing TiO2 NPs and polyallylamine (PAA) bearing poly(ethylene glycol) grafts through electrostatic interaction in aqueous medium. TiO2 NPs can generate reactive oxygen species (ROS) including singlet oxygen by sonication even after the entrapping into the micelles. PIC micelles could exhibit the cell killing effect by sonication after taken up into the cells, indicating the availability of TiO2 NPs-incorporated PIC micelles in SDT. However, since ROS have quite low life time, the generated ROS can show instantaneous cell killing effect. Therefore, the combination of transient SDT and persistent drugs should be an attractive strategy for more effective treatment. In this study, we demonstrated that TiO2 NPs-incorporated PIC micelles could also be used as drug carrier. It was recently found that TiO2 NPs-incorporated PIC micelles exhibit the effective multivalent anion condensation of PAA main chain. Zeta-potentials of PIC micelles in phosphate buffer and Tris/HCl buffer were quite different in spite of same pH and ion concentration, and phosphate ions effectively neutralized positive charges of PAA in the micelles due to counter ion condensation effect. On the basis of this effect, multivalent anionic molecules were effectively entrapped into the micelles. Furthermore, PIC micelles can deliver these multivalent anionic molecules into the cells. These results suggest that TiO2 NPs-incorporated PIC micelles have utilities as a carrier for multivalent anionic molecules. Also, the micelles can solubilize hydrophobic drugs, and the combination of cell killing effect by sonication to PIC micelles and various drug delivery might be applicable to a noninvasive and effective therapeutic approach.

Polyion complex micelle incorporating TiO2 nanoparticles for effective sonodynamic therapy

255th National Meeting (2018)

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