Folate receptor-targeted theranostic IrSx nanoparticles for multimodal imaging-guided combined chemo-photothermal therapy

Abstract

Nano-drug delivery systems with multi-modality imaging capacities are worth pursuing because they integrate diagnostic and therapeutic functions. Herein, we report the design, synthesis and evaluation of modified iridium sulfide (IrS_x) nanoparticles (NPs) for cancer therapy in vitro and in vivo. This nanosystem was prepared by modifying IrS_x with polyethylene glycol (PEG) conjugated to the targeting ligand folate (FA) for multimodal imaging-guided combined chemo-photothermal therapy. Upon PEG modification, the small IrS_x NPs (about 4 nm) self-assembled into much larger (about 120 nm) IrS_x-PEG-FA NPs, which exhibited high photostability, ideal photothermal effect, high drug loading and pH-/photothermal-responsive drug release properties. By using the model anticancer drug camptothecin (CPT), we demonstrated that CPT@IrS_x-PEG-FA can effectively target FA-receptor-positive cancer cells in vitro and show efficient tumor accumulation in vivo. The combination of CPT@IrS_x-PEG-FA treatment and irradiation with an 808 nm laser resulted in complete tumor elimination. Moreover, photothermal/photoacoustic (PA)/computed tomography (CT) imaging provided an effective means to monitor the therapeutic effects. Interestingly, the nanoparticles can be cleared, resulting in low systematic toxicity of CPT@IrS_x-PEG-FA. Our work demonstrates that the as-prepared IrS_x-PEG-FA NPs present a promising platform for the construction of multifunctional theranostic agents for cancer therapy.