pHLIP Technology
pHLIP® technology constitutes family of pH-Low Insertion Peptides, a novel class of pH-sensitive delivery agents, which selectively target and deliver diagnostic and therapeutic molecules to tumors. pHLIPs are linear peptides that sense cell-surface pH. They are moderately hydrophobic 25-35 aa peptides containing protonatable carboxyl groups. At normal pH, pHLIP peptides exist in unstructured, coil conformations in solution and at the surfaces of the membranes of normal cells. At the low surface pH of metabolically active cells, the negatively-charged residues become protonated. As a result, the hydrophobicity of the peptide increases, and triggers spontaneous membrane insertion, which is accompanied by the folding of the peptide to form a stable transmembrane helix. One terminus stays exposed to extracellular space and another terminus goes across membrane into cytoplasm.
pHLIP® Technology for Extracellular Delivery: pHLIP peptides can be used for extracellular targeted delivery of imaging and therapeutic payloads (small molecules and proteins) for decoration of cancer cells in tumors.
pHLIP® Technology for Intracellular Delivery: pHLIP peptides can be used for targeted intracellular delivery of therapeutic payloads (polar and moderately hydrophobic molecules) to cytoplasm of metabolically active cells.
pHLIP® Nanotechnology: Multiple pHLIP peptides can be used to decorate a single nanoparticle, which can range in size from a few to hundreds of nanometers. Nanocarriers decorated with pHLIP peptides are biocompatible, can target tumors, and demonstrate enhanced cellular uptake by cancer cells. Among the pHLIP peptide-coated nanoparticles that have been investigated are lipid, polymer and metal-based nanomaterials.
