Traditional drug sensitivity assay confirms the cell death by time-consuming fixation and labeling. This snapshot evaluation neglects valuable time-course details that may provide new insight for the speed-up of drug screening. Here we develop a label-free method to early report cell senescence by the endogenous lipofuscin autofluorescence. After drug treatment, we found the lipofuscin red autofluorescence greatly increased in apoptotic and necrotic cells. This approach allows the time-course observation of pharmacodynamics in 3D tumor organoids and could determine the drug sensitivity earlier than Annexin V/PI assay. This metabolic fluorescence hallmark could improve the throughput of drug sensitivity test.
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