SupraMolecular BioVectors (SMBV) improve antisense inhibition of erbB-2 expression.
New therapeutic strategies are now being developed against adenocarcinoma associated with erbB-2 amplification, particularly by inhibiting p185erbB-2 expression. Antisense oligodeoxynucleotides seem promising for this purpose as long as they are efficiently protected against degradation and targeted into the cells. We present antisense oligonucleotide carriers, the supramolecular biovectors (SMBVs), for which we have already demonstrated the ability to improve both cellular uptake and protection of oligodeoxynucleotide. The present work demonstrates that SMBVs elicit a specific and non-toxic action of antisense compounds in a cell model, irrespective of their sensitivity to nucleases. This is a major point, considering the specificity problems associated with the use of nuclease-resistant phosphorothioate oligodeoxynucleotide. SMBVs improve antisense efficiency of oligodeoxynucleotide designed against p185erbB-2, with a complete growth arrest of SK-Br-3, human adenocarcinoma mammary cells that overexpress p185erbB-2 and no effect on MCF-7 cells that normally express p185erbB-2. The comparison of SMBVs with DOTAP reveals the statistically higher efficiency of SMBVs, which allows the antisense inhibition of p185erbB-2 expression in 65-75% of SK-Br-3 cells (P < 0.05). The efficiency and controlled synthesis of SMBVs underline their potentialities as oligodeoxynucleotide carriers for in vivo experiments.
Allal
C
C
Laboratoire d'Oncologie Cellulaire et Moléculaire, EA 2048 MRES, Faculté des Sciences Pharmaceutiques and Centre de Lutte Contre le Cancer Claudius Regaud, Toulouse, France.
Sixou
S
S
Kravtzoff
R
R
Soulet
N
N
Soula
G
G
Favre
G
G
D002455:Cell Division / Q000187:drug effects; D003851:Deoxyribonucleases / Q000378:metabolism; D005069:Evaluation Studies as Topic; D018734:Genes, erbB-2 / Q000187:drug effects*; D005822:Genetic Vectors / Q000235:genetics*; D006801:Humans; D016376:Oligonucleotides, Antisense / Q000235:genetics* / Q000494:pharmacology; D014176:Protein Biosynthesis / Q000187:drug effects; D012333:RNA, Messenger / Q000187:drug effects* / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000187:drug effects* / Q000378:metabolism; D014407:Tumor Cells, Cultured
D003851:Deoxyribonucleases; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D018719:Erb-b2 Receptor Tyrosine Kinases