Dual-stimuli responsive nanotheranostics for mild hyperthermia enhanced inhibition of Wnt/β-catenin signaling

Wnt/beta-catenin signaling cascade is highly associated with tumorigenesis and progression of various cancers. Targeting Wnt/beta-catenin signaling exhibits a promising way for cancer treatment. Herein, dual-stimuli responsive nanotheranostics was synthesized, which was composed of melanin coated magnetic nanoparticles (MMNs) and Wnt signaling inhibitor obatoclax (OBX) for multimodality imaging guided mild hyperthermia-enhanced chemotherapy. The MMNs could be used as contrast agents for magnetic resonance imaging (MRI) and photoacoustic imaging (PAI) guided photothermal therapy. In addition, OBX-loaded MMNs (OBX-MMNs) were specific response to both pH changes and near-infrared (NIR) light illumination, which could trigger OBX release. Most intriguingly, tumor tissue accumulation and cellular intemalization of this nanotheranostics could be dramatically enhanced through mild hyperthermia generated by laser-irradiated MMNs. Laser irradiation exhibited efficient chemotherapeutic outcome through enhancing OBX-mediated inhibition of the Wnt/beta-catenin signaling. Our results indicated the as-prepared OBX-MMNs hold great potential for MR/PA dual-modal imaging guided mild hyperthermia-enhanced chemotherapy.