Multifunctional Polypyrrole-Coated Mesoporous TiO2 Nanocomposites for Photothermal, Sonodynamic, and Chemotherapeutic Treatments and Dual-Modal Ultrasound/Photoacoustic Imaging of Tumors

: TiO2 nanoparticles have emerged as satisfactory sonosensitizers in sonodynamic therapy over the years, but shortcomings such as poor drug loading capability and inadequate techniques to construct suitable TiO2 nanoparticles, limit their broader applications. Hence, in this paper, versatile nanocomposites that combine mesoporous TiO2 nanoparticles (mTiO2 s) with the promising photothermal material, polypyrrole (PPY) to exert synergistic therapeutic effects on tumors are fabricated. The PPY-coated mesoporous TiO2 nanocomposites (mTiO2 @PPYs) act as drug delivery vehicles and ultrasonically activated sonosensitizers as well as photothermal agents. Besides, mTiO2 @PPY may have potential as an ultrasound/photoacoustic (US/PA) imaging contrast agent. The mTiO2 @PPY shows a favorable drug loading and good photothermal conversion ability. Moreover, intracellular reactive oxygen species generation is verified. The in vitro cell experiments on HepG2 and 4T1 cells demonstrate that honokiol (HNK)-loaded mTiO2 @PPY has satisfactory cytotoxicity under laser and US irradiation, and the results are further validated by animal experiments. The ability of mTiO2 @PPY as a contrast agent for US and PA imaging is investigated both in vitro and in vivo. The results indicate that mTiO2 @PPY-HNK has multitherapeutic effects and bimodal imaging property, which shows great prospect as a novel nanosystem in antitumor applications.