Their ‘cargo carrier’ peptide, named pHLIP, accumulates in the membranes of cells in acidic environments and spontaneously transfers attached molecules across the membrane. The cargo is then released by cleavage of a sulfur-sulfur bond that is only unstable if it is inside the cell.
The study, which was published in the Proceedings of the National Academy of Sciences, shows that pHLIP entry into the cell membrane and the translocation of molecules into cells are not mediated by the usual entry pathways – endocytosis, interactions with cell receptors, or by formation of pores in cell membranes.
“Our system offers a new technology for the fast and efficient delivery of drugs, imaging probes, or cell and gene regulation agents into living cells,” said Donald Engelman, professor of molecular biophysics and biochemistry at Yale. “pHLIP may provide a new approach for imaging, diagnosis and treatment of diseases with naturally occurring or artificially created low-pH extracellular environments, such as tumors, infarcts, stroke-afflicted tissue, atherosclerotic lesions, sites of inflammation or infection, or damaged tissue resulting from trauma.”