Raman-guided subcellular pharmaco-metabolomics for metastatic melanoma

Abstract

We utilized Raman spectro-microscopy to non-invasively probe metabomics within single live cells, aiming to identify druggable metabolic susceptibilities from a series of patient-derived BRAF mutant melanoma cell lines. Each cell line represents a phenotype with different characteristic level of de-differentiation and BRAFi (BRAF inhibitor) resistance. First, with single-cell Raman spectroscopy and stimulated Raman scattering (SRS) microscopy, followed by transcriptomics anal., we identified lipid processes as major metabolic functional difference between different phenotypes. We then utilized hyperspectral-SRS imaging on intracellular single organelles to identify a previously unknown susceptibility of lipid desatn. within de-differentiated cell lines. Drugging this target leads to cellular apoptosis accompanied by phase sepd. intracellular domains. The integration of subcellular Raman spectro-microscopy with lipidomics and transcriptomics suggests highly heterogenous metabolic responses and possible lipid regulatory mechanisms underlying this pharmacol. treatment. Our method should provide a general approach in spatially-resolved single cell metabolomics studies.

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