Nano Science and Technology Institute
Nanotech 2006 Vol. 2
Nanotech 2006 Vol. 2
Technical Proceedings of the 2006 NSTI Nanotechnology Conference and Trade Show, Volume 2
Chapter 1: Cancer Nanotechnology

Injection of Molecules into Cells using a pH-Triggered Molecular Nanosyringe

Authors:O.A. Andreev, S. Sandugu, D.M. Engelman and Y.K. Reshetnyak
Affilation:University of Rhode Island, US
Pages:57 - 60
Keywords:transmembrane peptide, helix, phalloidin, acidity
Abstract: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 injection is driven by a water-soluble peptide, pHLIP (pH (Low) Insertion Peptide), that inserts itself into the plasma membrane at pH < 7.0 and forms a transbilayer helix with its C-terminus in the cytoplasm. A therapeutic or imaging agent bound to the C- terminus via a disulfide link is delivered to the cytoplasm, where the reducing environment cleaves the disulfide, releasing the agent. We show the injection of fluorescent dyes into cancer cells at pH 5.5-6.5, whereas only traces of dye are observed on the outer side of the membrane at pH 7.4. We demonstrate that the cell-impermeable toxin phalloidin, attached to pHLIP by an S-S bond, is translocated and released, inducing stabilization of the actin cytoskeleton and inhibition of cell contractility. However, phalloidin irreversibly bound to pHLIP does not stain actin filaments, but labels the cell membrane at low pH and can be washed out at physiological pH. The nanosyringe could be used to deliver drugs to cells in the acidic environment that is created in cancer tissue.
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