Leland Stanford Junior University

Kanyi Pu

Jianghong Rao

Adam Shuhendler

Encompassed are embodiments of activatable nanoprobes useful for in vivo longitudinal imaging of drug hepatotoxicity with oxidative and nitrosative stress as the safety biomarkers. Both HOand ONOOare important mediators of radical stress. Two channels of optical detection, intrinsically free from cross-talk, were engineered into superconducting polymer nanoparticles to generate chemiluminescence resonance energy transfer between the conjugated polymer matrix of the nanoparticle and an incorporated chemiluminescent substrate allowing for the luminescent detection of HOand fluorescence resonance energy transfer between the polymer matrix and an oxidation-degradable fluorophore for ratiometric detection of ONOO These nanoprobes have been applied for real-time in vivo monitoring of hepatotoxicity resulting from challenges from drugs. In addition to the ability of imaging the dose-dependence of oxidative and nitrosative stress, the positive detection of radical stress that precedes histological changes allow the early and longitudinal detection of drug-induced hepatotoxicity in vivo.

Discrete imaging of hepatic oxidative and nitrosative stress with two-channel nanoparticles for in vivo drug safety screening

For whole animal in-situ and real-time imaging of inflammation, a dual-color fluorescent nanoprobe is provided for the detection of reactive oxygen and nitrogen species (RONS) in inflammatory microenvironments. The nanoprobes of the disclosure are a RONS-responsive energy transferring nanosystem of a fluorescent conjugated polymer core and a PEG-shell linked with RONS-sensing antennae as a FRET acceptor. These nanoprobes allow in vivo imaging of the entire process of inflammation from the release of local tissue distress signals, to the action of leukocytes and macrophages late in the process of inflammation, through to restitution, allowing in whole-body diagnosis and monitoring of inflammatory diseases.

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Mountain View, CA, United States of America

Kanyi Pu