title: Liposome-coated lipoplex-based carrier for antisense oligonucleotides.
abstract: The chemical nature of genetic drugs (e.g. antisense oligonucleotides, siRNA, vectors) requires a suitable carrier system to protect them from enzymatic degradation without changing their properties and enable efficient delivery into target cells. Lipid vectors for nucleic acid delivery that have been widely investigated for years can be very effective. As the majority of attempts made in the field of cancer gene therapy have focused on solid tumors, while blood cancer cells have attracted less attention, the latter became the subject of our investigation. The lipid carrier proposed here is based on liposomes constructed by others but the lipid composition is original. A liposome-coated lipoplex (L-cL) consists of a core arising from complexation of positively charged lipid and negatively charged oligodeoxynucleotide (ODN) or plasmid DNA coated by a neutral or anionic lipid bilayer. Moreover, our lipid vector demonstrates size stability and is able to retain a high content of enclosed plasmid DNA or antisense oligodeoxynucleotides (asODNs). Observed transfection efficacies of the tested preparation using a plasmid coding for fluorescent protein were up to 60-85% of examined leukemia cells (Jurkat T and HL-60 lines) in the absence or the presence of serum. When BCL‑2 asODN was encapsulated in the L-cL, specific silencing of this gene product at both the mRNA and protein level and also a markedly decreased cell survival rate were observed in vitro. Moreover, biodistribution analysis in mice indicates prolonged circulation characteristic for PEG-modified liposomal carriers. Experiments on tumor-engrafted animals indicate substantial inhibition of tumor growth.
authors.affiliation: a Laboratory of Cytobiochemistry; Biotechnology Faculty ; University of Wrocław ; Wrocław , Poland.
authors.forename: Paulina
authors.initials: P
authors.lastname: Wyrozumska
authors.forename: Justyna
authors.initials: J
authors.lastname: Meissner
authors.forename: Monika
authors.initials: M
authors.lastname: Toporkiewicz
authors.forename: Marta
authors.initials: M
authors.lastname: Szarawarska
authors.forename: Kazimierz
authors.initials: K
authors.lastname: Kuliczkowski
authors.forename: Maciej
authors.initials: M
authors.lastname: Ugorski
authors.forename: Marta A
authors.initials: MA
authors.lastname: Walasek
authors.forename: Aleksander F
authors.initials: AF
authors.lastname: Sikorski
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D004195:Disease Models, Animal; D004337:Drug Carriers / Q000737:chemistry; D004355:Drug Stability; D005260:Female; D019254:Genes, bcl-2; D006801:Humans; D008081:Liposomes / Q000737:chemistry; D008297:Male; D051379:Mice; D016376:Oligonucleotides, Antisense / Q000008:administration & dosage* / Q000737:chemistry / Q000235:genetics / Q000493:pharmacokinetics; D014018:Tissue Distribution; D014162:Transfection; D023041:Xenograft Model Antitumor Assays
chemical_list: D004337:Drug Carriers; D008081:Liposomes; D016376:Oligonucleotides, Antisense
keywords: AML, acute myeloid leukemia; BCL-2 gene; Bcl-2, B-cell lymphoma 2 protein; CCL, coated cationic liposomes; DC-CHOL, 3β-(N-[dimethylaminoethane]carbamoyl)cholesterol) DiD-1,1′, dioctadecyl-3,3,3′, 3′-tetramethylindodicarbocyanine; DOPE, 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine); DOTAP, 1, 2-dioleoyl-3-trimethylammonium-propane); DSPE, PEG-(1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)2000] (ammonium salt); GFP, green fluorescent protein; HPC, hydrogenated egg phosphatidylcholine); L-cL, liposome-coated lipoplex; PE/PC, phosphatidylethanolamine and phosphatidylcholine liposomes; acute leukemia; antisense deoxynucleotides; asODN, antisense oligodeoxynucleotide; cationic lipids; gene therapy; lipid carrier; lipoplex; liposome coated lipoplex; pDNA, plasmid DNA; siRNA, small interferingRNA TGI, tumor growth inhibition