Multifunctional FeS2 theranostic nanoparticles for photothermal-enhanced chemodynamic/photodynamic cancer therapy and photoacoustic imaging

Chemodynamic therapy (CDT) and photodynamic therapy (PDT) mediated by reactive oxygen species (ROS) hold great potential for cancer therapy. However, they are still limited by rigorous reaction conditions of efficacious Fenton reaction, reliance on oxygen, and inherent defects of traditional common photosensitizers (PSs). Herein, we reported an L-Buthionine-sulfoximine (BSO) modified FeS2 nanoparticles (BSO-FeS2 NPs) with enhanced ROS generation under single wavelength (808 nm) laser irradiation. First, FeS2 NPs showed high photothermal conversion efficiency (49.5%) and enhanced O2− and OH generation capability via direct electron transfer presenting photothermal-improved Fenton reaction and photocatalytic ability. With the BSO modification, BSO-FeS2 NPs could inhibit the synthesis of glutathione (GSH) and accelerate the accumulation of ROS, which further enhanced the PDT/CDT treatment efficacy and resulted in high in vivo tumor inhibition rate (95%). Second, BSO-FeS2 NPs could activate the repolarization of macrophages from M2 to M1 for potential tumor immunotherapy. Last, BSO-FeS2 NPs showed good performance on photoacoustic imaging (PAI). All these results establish the capability of BSO-FeS2 NPs as nano-theranostic agents in PAI guided PTT/CDT/PDT combination therapy for cancer treatment.