Renal-Clearable Ultrasmall Polypyrrole Nanoparticles with Size-Regulated Property for Second Near-Infrared Light-Mediated Photothermal Therapy

The critical issue that hinders the translation of nanomaterials from basic research to clinical trials is their potential toxicity caused by long-term body retention. It is still a huge challenge to integrate renal-clearable and theranostic properties into one nanomedicine, especially exploring the nanomaterials with optical absorption in the second near-infrared light (NIR II) biowindow with deep penetration and less tissue scattering. Here, ultrasmall polypyrrole (PPy, ≈2 nm)-based theranostic agents via a facile and green one-step method, which exhibit fluorescence (FL)/photoacoustic (PA)/NIR II multimodal imaging, superior photostability, as well as high photothermal conversion efficiency of 33.35% at 808 nm and 41.97% at 1064 nm is developed. Importantly, these ultrasmall PPy-PEG nanoparticles (NPs) reveal abundant tumor accumulation and efficient renal clearance. Both in vitro and in vivo studies indicate that ultrasmall PPy-PEG NPs have excellent photothermal effect under NIR II laser irradiation that can effectively eliminate the tumors with extremely low systemic toxicity.