title: pH dependent transfer of nano-pores into membrane of cancer cells to induce apoptosis.
abstract: Proper balance of ions in intracellular and extracellular space is the key for normal cell functioning. Changes in the conductance of membranes for ions will lead to cell death. One of the main differences between normal and cancerous cells is the low extracellular pHe and the reverse pH gradient: intracellular pHi is higher than extracellular pHe. We report here pH-selective transfer of nano-pores to cancer cells for the dis-regulation of balance of monovalent cations to induce cell death at mildly acidic pHe as it is in most solid tumors. Our approach is based on the pH-sensitive fusion of cellular membrane with the liposomes containing gramicidin A forming cation-conductive β-helix in the membrane. Fusion is promoted only at low extracellular pH by the pH (Low) Insertion Peptide (pHLIP®) attached to the liposomes. Gramicidin channels inserted into the cancer cells open flux of protons into the cytoplasm and disrupt balance of other monovalent cations, which induces cell apoptosis.
authors.affiliation: 1] Physics Department, University of Rhode Island, 2 Lippitt Road, Kingston, RI 02881, USA [2].
authors.forename: Dayanjali
authors.initials: D
authors.lastname: Wijesinghe
authors.affiliation: 1] Physics Department, University of Rhode Island, 2 Lippitt Road, Kingston, RI 02881, USA [2].
authors.forename: Mohan C M
authors.initials: MC
authors.lastname: Arachchige
authors.affiliation: Physics Department, University of Rhode Island, 2 Lippitt Road, Kingston, RI 02881, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Lu
authors.affiliation: Physics Department, University of Rhode Island, 2 Lippitt Road, Kingston, RI 02881, USA.
authors.forename: Yana K
authors.initials: YK
authors.lastname: Reshetnyak
authors.affiliation: Physics Department, University of Rhode Island, 2 Lippitt Road, Kingston, RI 02881, USA.
authors.forename: Oleg A
authors.initials: OA
authors.lastname: Andreev
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D001692:Biological Transport / Q000187:drug effects; D002414:Cations, Monovalent / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000473:pathology; D049109:Cell Proliferation; D006096:Gramicidin / Q000494:pharmacology*; D006367:HeLa Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008081:Liposomes / Q000494:pharmacology*; D008928:Mitochondria / Q000473:pathology; D009369:Neoplasms / Q000473:pathology*
chemical_list: D000900:Anti-Bacterial Agents; D002414:Cations, Monovalent; D008081:Liposomes; D006096:Gramicidin