MALDI-TOF mass spectrometry: A powerful tool to study the internalization of cell-penetrating peptides

This review summarizes the contribution of MALDI-TOF mass spectrometry in the study of cell-penetrating peptide (CPP) internalization in eukaryote cells. This technique was used to measure the efficiency of cell-penetrating peptide cellular uptake and cargo delivery and to analyze carrier and cargo intracellular degradation. The impact of thiol-containing membrane proteins on the internalization of CPP–cargo disulfide conjugates was also evaluated by combining MALDI-TOF MS with simple thiol-specific reactions. This highlighted the formation of cross-linked species to cell-surface proteins that either remained trapped in the cell membrane or led to intracellular delivery. MALDI-TOF MS is thus a powerful tool to dissect CPP internalization mechanisms.