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.