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

Abstract

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. <i>In vitro</i> 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 <i>in vivo</i> 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.