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

Abstract 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.