title: pHLIP®-mediated delivery of PEGylated liposomes to cancer cells.
abstract: We develop a method for pH-dependent fusion between liposomes and cellular membranes using pHLIP® (pH Low Insertion Peptide), which inserts into lipid bilayer of membrane only at low pH. Previously we establish the molecular mechanism of peptide action and show that pHLIP can target acidic diseased tissue. Here we investigate how coating of PEGylated liposomes with pHLIP might affect liposomal uptake by cells. The presence of pHLIP on the surface of PEGylated-liposomes enhanced membrane fusion and lipid exchange in a pH dependent fashion, leading to increase of cellular uptake and payload release, and inhibition of cell proliferation by liposomes containing ceramide. A novel type of pH-sensitive, "fusogenic" pHLIP-liposomes was developed, which could be used to selectively deliver various diagnostic and therapeutic agents to acidic diseased cells.
authors: Physics Department, University of Rhode Island, 2 Lippitt Road, Kingston, RI 02881, USA.
authors: Lan
authors: L
authors: Yao
authors: Jennifer
authors: J
authors: Daniels
authors: Dayanjali
authors: D
authors: Wijesinghe
authors: Oleg A
authors: OA
authors: Andreev
authors: Yana K
authors: YK
authors: Reshetnyak
mesh_terms: D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002518:Ceramides / Q000008:administration & dosage; D004705:Endocytosis; D005456:Fluorescent Dyes / Q000008:administration & dosage; D006046:Gold / Q000737:chemistry; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008081:Liposomes / Q000737:chemistry*; D008565:Membrane Proteins / Q000737:chemistry*; D053768:Metal Nanoparticles / Q000737:chemistry; D009369:Neoplasms / Q000378:metabolism*; D011092:Polyethylene Glycols / Q000737:chemistry
chemical_list: D002518:Ceramides; D005456:Fluorescent Dyes; D008081:Liposomes; D008565:Membrane Proteins; C533201:pHLIP protein; D011092:Polyethylene Glycols; D006046:Gold