A NO-Responsive Ratiometric Fluorescent Nanoprobe for Monitoring Drug-Induced Liver Injury in the Second Near-Infrared Window.

Abstract

Currently, drug-induced liver injury (DILI) has become a huge concern for the majority of modern medicine, whereas the diagnosis of DILI is still in its infancy due to the lack of appropriate methods. Herein, based on the fact that nitric oxide (NO) has been recognized as an early unifying, direct, and vital biomarker for DILI, we rationally designed and developed a NO-responsive ratiometric fluorescent nanoprobe DCNP@MPS@IR NO to quantitatively detect NO and monitor DILI in the second near-infrared (NIR-II) window. In the presence of NO, due to the conversion of IR NO into IR RA and excellent stability of the downconversion nanoparticle (DCNP), DCNP@MPS@IR NO could present a "Turn-On" fluorescence signal at 1050 nm under 808 nm excitation (F1050Em,808Ex) and an "Always-On" fluorescence signal at 1550 nm under 980 nm excitation (F1550Em,980Ex), which led to a "Turn-On" ratiometric fluorescence signal F1050Em,808Ex/F1550Em,980Ex. DCNP@MPS@IR NO was then successfully applied in vitro to selectively detect NO, at a linear concentration range of 0-100 μM with a limit of detection of 0.61 μM. In vivo results revealed that DCNP@MPS@IR was available to quantify NO in acetaminophen (APAP)-induced liver injury, monitor DILI, and screen an antidote for APAP through NIR-II ratiometric fluorescence imaging. We envision that our nanoprobe DCNP@MPS@IR NO might become a really useful biotechnology tool for visualizing and early diagnosis of drug-induced liver injury and revealing the mechanism of drug hepatotoxicity in the clinic in the near future.