Biodegradable Self‐Assembled Ultrasmall Nanodots as Reactive Oxygen/Nitrogen Species Scavengers for Theranostic Application in Acute Kidney Injury

Acute kidney injury (AKI) is frequently triggered by abundant reactive oxygen/nitrogen species (RONS) and leads to high morbidity and mortality in clinic. Unfortunately, the current clinical treatment options are only limited to supportive care, and hence, the development of nano-antioxidants with high kidney enrichment is an attractive novel strategy for AKI management. Herein, self-assembled ultrasmall nanodots are reported that consist of iron ion, gallic acid, and polyvinylpyrrolidone (denoted as FGP nanodots) as broad-spectrum RONS scavengers to alleviate both glycerinum- and cis-platinum- induced AKI in mice. Ultrasmall FGP nanodots (≈3.5 nm) offer efficient protection in vitro and reduce cellular apoptosis after H2 O2 stimulation by eliminating various RONS including hydroxyl radical (·OH), superoxide anion (·O2- ), nitric oxide (NO), and peroxynitrite (ONOO- ), etc. In vivo duplex magnetic resonance/fluorescence imaging demonstrates preferential accumulation of FGP nanodots in the kidneys with rapid renal clearance through urine. Importantly, FGP nanodots exhibit remarkable RONS consumption in vivo with enhanced biocompatibility and biodegradability, resulting in superior therapeutic effect than small molecule drug (Amifostine) in two AKI mouse models. This study presents the promising potential of ultrasmall self-assembled FGP nanodots as imaging contrast agent and broad-spectrum antioxidant nanomedicine for AKI theranotics.