Fluorescence-detected mid-infrared photothermal (F-MIP) imaging reveals a metabolic signature of drug resistance in ovarian cancer cells

Drug resistance remains a major challenge in effective ovarian cancer therapy, and the associated metabolic adaptations are highly heterogeneous and difficult to resolve at the single-cell level. Here, we present fluorescence-detected mid-infrared photothermal microscopy (F-MIP) as a sensitive imaging platform to reveal metabolic signatures associated with drug resistance in cancer cells. Applying F-MIP to ovarian cancer platinum-sensitive and resistant models, we identify a distinct metabolic phenotype in drug-resistant cells characterized by significant changes in the mid-infrared fingerprint region. These metabolic changes occur concomitantly with the development of drug resistance. By leveraging fingerprint-region contrast, F-MIP captures early metabolic signatures that highlight lipid metabolic pathways as potential targets for addressing cancer drug resistance.