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

Abstract

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. (C) 2022 The Korean Society of Industrial and Engineering Chemistry. Published by Elsevier B.V. All rights reserved.