Injection of Molecules into Cells using a pH-Triggered Molecular Nanosyringe
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We have engineered a molecular nanosyringe that enables injection of molecules into a target cell at acidic pH, but not at normal, physiological pH. The nanosyringe consists of a water-soluble membrane peptide (pHLIP ‐ pH (Low) Insertion Peptide), a link and a cargo molecule. Injection is driven by pHLIP, which inserts as a heli x across the cell membrane and translocates one of its termini into the cytoplasm. The peptide does not exhibit any elements of secondary structure in solution or when loosely bound on the cell membrane at neutral pH. We show the injection of cell-impermeable molecules into cancer cells at pH6.5. T he nanosyringe offers a novel technology for selective de livery of cargo-molecules into cancer cells by exploiting the acidic extracellular environment that is a characterist ic feature of many tumors.
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