Liposome-coated lipoplex-based carrier for antisense oligonucleotides.
Cancer Biol Ther
; 16(1): 66-76, 2015.
Article
de En
| MEDLINE
| ID: mdl-25482931
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 BCL2 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.
Mots clés
AML, acute myeloid leukemia; BCL-2 gene; Bcl-2, B-cell lymphoma 2 protein; CCL, coated cationic liposomes; DC-CHOL, 3ß-(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
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Vecteurs de médicaments
/
Oligonucléotides antisens
/
Liposomes
Type d'étude:
Prognostic_studies
Limites:
Animals
/
Female
/
Humans
/
Male
Langue:
En
Journal:
Cancer Biol Ther
Sujet du journal:
NEOPLASIAS
/
TERAPEUTICA
Année:
2015
Type de document:
Article
Pays d'affiliation:
Pologne