Synthesis of Methotrexate-Loaded Dumbbell-Shaped Titanium Dioxide/Gold Nanorods Coated with Mesoporous Silica and Decorated with Upconversion Nanoparticles for Near-Infrared-Driven Trimodal Cancer Treatment

This study prepared dumbbell-shaped titanium dioxide (TiO₂)/gold nanorods (AuNRs) coated with mesoporous silica shells (mS) (AuNRs-TiO₂@mS). Methotrexate (MTX) was further loaded into the AuNRs-TiO₂@mS, and then upconversion nanoparticles (UCNPs) were decorated to form AuNRs-TiO₂@mS-MTX: UCNP nanocomposites. TiO₂ is used as an intense photosensitizer (PS) to produce cytotoxic reactive oxygen species (ROS), leading to photodynamic therapy (PDT). Concurrently, AuNRs exhibited intense photothermal therapy (PTT) effects and photothermal conversion efficiency. In vitro results suggested that these nanocomposites can kill oral cancer cells (HSC-3) without toxicity through irradiation of NIR laser, owing to the synergistic effect. The in vivo studies indicated that these nanocomposites exhibited excellent antitumor effects through synergistic PDT/PTT/chemotherapy under a near-infrared (NIR) 808 nm laser irradiation. Thus, these AuNRs-TiO₂@mS: UCNP nanocomposites have great potential to undergo deep tissue penetration with enhanced synergistic effects through NIR-triggered light for cancer treatment.