Lipid droplet-specific NIR fluorescent probe with large Stokes shift for assessing the effect of chronic drugs on drug-induced liver injury

Drug-induced liver injury (DILI) is secondary to drug-induced hepatitis, resulting in damage or necrosis of liver cells and even liver failure. Assessing whether chronic medications induce liver injury and which medications are most likely to be the culprits is challenging. However, current biochemical and imaging diagnostic methods fail to detect this subclinical manifestation. Recent studies proved that the development of DILI is associated with dysfunction of lipid droplets (LDs). This is why we designed, in this paper, a new LDs-specific fluorescent probe (CF-PN) to monitor this biological process and evaluate the effects of relevant drugs on DILI. Interestingly, we found that DILI induced a significant increase in viscosity not only at the cellular level, but also in vivo. Such increase of LDs viscosity was related to lipase activity. More importantly, drug reviews have shown that chronic medications used to treat psychosis (droperidol, decafenazine, amitriptyloine, chlorpromazine, trifluoperazine, and chlorprothixene), heart disease (mexiletine), hyperlipidaemia (simvastatin, bezafibrate, niacin, and acipimox), and hypertension (aspirin, dexamethasone, losartan, olmesartan, and candesartan) can all exacerbate the DILI, while the haloperidol for psychosis and the resveratrol for hyperlipidaemia can alleviate DILI to a certain extent. In conclusion, our work provides an effective method for medical diagnosis and drug safety assessment of DILI.