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Nanoprobes for in vivo drug toxicity imaging


Stanford Reference:

13-260


Abstract


Researchers in Dr. Jianghong Rao’s lab have developed nanoprobes for monitoring drug-induced hepatotoxicity in vivo in real time. Drug toxicity is a long-standing concern of modern medicine. Oxidative and nitrosative stress underlie drug toxicity due to the metabolic bioactivation of drugs to reactive metabolites. The liver is the organ most frequently affected. In addition to effects on the end-user, drug-induced hepatotoxicity is the single most important cause of both FDA non-approval and drug withdrawal from the market. Current preclinical methods to predict drug toxicity are limited as they cannot be used in live animals and do not analyze biomarkers that are mechanistically linked to the toxicity of the parent drug compound. To overcome this limitation, the inventors designed this nanoprobe which measures oxidative and nitrosative stress and thus can uniquely image drug toxicity in real time in live animals.

Stage of research
The nanoprobe was used in mice for real-time in vivo monitoring of hepatotoxicity following challenge with two known hepatotoxic drugs. The imaging results were validated with histological analysis.


Applications


  • Drug development
    • Drug safety screening
      • Screen new drugs or chemical entities for their propensity to produce hepatic oxidative or nitrosative stress
    • Drug toxicity studies
      • Obtain mechanistic information about drug toxicity
      • Selection of remediation strategies
      • Aid in redesign of drug candidates
  • Basic research

Advantages


  • Superior optical reporter
    • Resistant to oxidative chemical bleaching effects (unlike quantum dots or small molecule fluorophores)
    • Stable
    • Biocompatible
    • Permits longitudinal studies in vivo
  • Simultaneously and differentially detect two sources of toxicity to permit
    • More comprehensive toxicity screens
    • More robust assessment of mechanism of toxicity
  • Can be tailored for specific analyte detection and for targeting to specific organ of interest
  • Reduce risk in drug development
  • Improve therapeutic outcomes and patient safety

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Date Released

 1/28/2015
 

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Irit Gal, Senior Licensing Associate
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Related Keywords


medical devices: imaging   hepatic   research tool: reagent   screening: screen   drug development   drug monitoring   drug screening   optical imaging   optical imaging agent   pharmaceutical safety   research tool: imaging   therapeutic: drug design   therapeutic: imaging   tissue imaging   preclinical drug screening   therapeutic: metabolism   
 

   

  

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