Fluoro-Photoacoustic Polymeric Renal Reporter for Real-Time Dual Imaging of Acute Kidney Injury

Adv Mater. 2020 Apr;32(17):e1908530. doi: 10.1002/adma.201908530. Epub 2020 Mar 6.

Abstract

Photoacoustic (PA) imaging agents detect disease tissues and biomarkers with increased penetration depth and enhanced spatial resolution relative to traditional optical imaging, and thus hold great promise for clinical applications. However, existing PA imaging agents often encounter the issues of slow body excretion and low-signal specificity, which compromise their capability for in vivo detection. Herein, a fluoro-photoacoustic polymeric renal reporter (FPRR) is synthesized for real-time imaging of drug-induced acute kidney injury (AKI). FPRR simultaneously turns on both near-infrared fluorescence (NIRF) and PA signals in response to an AKI biomarker (γ-glutamyl transferase) with high sensitivity and specificity. In association with its high renal clearance efficiency (78% at 24 h post-injection), FPRR can detect cisplatin-induced AKI at 24 h post-drug treatment through both real-time imaging and optical urinalysis, which is 48 h earlier than serum biomarker elevation and histological changes. More importantly, the deep-tissue penetration capability of PA imaging results in a signal-to-background ratio that is 2.3-fold higher than NIRF imaging. Thus, the study not only demonstrates the first activatable PA probe for real-time sensitive imaging of kidney function at molecular level, but also highlights the polymeric probe structure with high renal clearance.

Keywords: acute kidney injury; kidney imaging; optical probes; photoacoustic imaging.

MeSH terms

  • Acute Kidney Injury / chemically induced
  • Acute Kidney Injury / diagnostic imaging*
  • Acute Kidney Injury / metabolism
  • Acute Kidney Injury / pathology
  • Animals
  • Biomarkers / blood
  • Cell Line
  • Cell Nucleus / chemistry
  • Cell Nucleus / metabolism
  • Cisplatin / toxicity
  • Creatinine / blood
  • Fluorescent Dyes / chemistry*
  • Fluorescent Dyes / metabolism
  • Humans
  • Kidney / diagnostic imaging
  • Kidney / pathology
  • Mice
  • Microscopy, Fluorescence
  • Photoacoustic Techniques / methods*
  • Signal-To-Noise Ratio
  • Spectrophotometry, Ultraviolet
  • gamma-Glutamyltransferase / blood
  • gamma-Glutamyltransferase / metabolism

Substances

  • Biomarkers
  • Fluorescent Dyes
  • Creatinine
  • gamma-Glutamyltransferase
  • Cisplatin