pH-responsive phototherapeutic poly(acrylic acid)-calcium phosphate passivated TiO2 nanoparticle-based drug delivery system for cancer treatment applications

This paper reports the hydrothermal synthesis and characterization of poly(acrylic acid)-calcium phosphate passivated TiO2 nanoparticles (TiO2@PAA-CaP NPs). The efficient loading and release of doxorubicin (DOX) from the TiO2@PAA-CaP NPs was observed at pH = 7.4 and 5.2, respectively. The loading and encapsulation amount of DOX in TiO2@PAA-CaP NPs was approximately fifteen and eight times as large as that of unfunctionalized TiO2 NPs, respectively, suggesting the PAA-CaP passivation layer enhanced the interaction between DOX and TiO2@PAA-CaP NPs. The DOX-loaded TiO2@PAA-CaP (TiO2@PAA-CaP(DOX)) NPs exhibited much faster cumulative DOX release at acidic pH = 5.2 than at neutral pH = 7.4 because of the pH-responsive dissolution properties of the PAA-CaP passivation layer. TiO2@PAA-CaP(DOX) NPs showed higher cytotoxicity towards MCF-7 tumor cells than free DOX. Confocal fluorescence microscopy and flow cytometry confirmed the enhanced cellular uptake of TiO2@PAA-CaP(DOX) NPs followed by the intracellular release of DOX. Overall, TiO2@PAA-CaP(DOX) NPs demonstrated significantly higher total cytotoxicity towards MCF-7 tumor cells under UV-A irradiation, which was attributed to a synergistic effect between efficient DOX delivery and enhanced photoinduced reactive oxygen species (ROS) generation. This study provides a facile means of synthesizing TiO2-based multifunctional nanocarriers with pH-responsive drug delivery and ROS generation essential for high efficacy therapeutic applications in cancer treatments.