Water-soluble carbosilane dendrimers protect phosphorothioate oligonucleotides from binding to serum proteins.
Treatment of dendriplexes formed between water-soluble carbosilane dendrimers and phosphorothioate oligodeoxynucleotides (ODN) with the anionic detergent sodium dodecyl sulfate disrupted the complexes indicating that the nature of the union in such dendriplexes is merely electrostatic. However, dendriplexes were not dissociated by serum proteins like bovine or human serum albumins, as assessed by gel electrophoresis and fluorescence experiments. This would imply a dendrimer-mediated protective effect able to prevent ODN interactions with serum proteins and additionally could translate into a reduction of the ODN doses needed to achieve the biological effects. The employment of carbosilane dendrimers as carriers may solve the problem of ODN kidnapping by plasmatic proteins as a key drawback for therapeutics involving ODNs. As examples, transfection processes on normal primary peripheral blood cells and diagnosis of HIV infection in the presence of serum have been assayed.
Chonco
Louis
L
Laboratorio de Inmunobiología Molecular, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
Bermejo-Martín
Jesus F
JF
Ortega
Paula
P
Shcharbin
Dzmitry
D
Pedziwiatr
Elzbieta
E
Klajnert
Barbara
B
de la Mata
F Javier
FJ
Eritja
Ramon
R
Gómez
Rafael
R
Bryszewska
Maria
M
Muñoz-Fernandez
Ma Angeles
MA
D000818:Animals; D002417:Cattle; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003588:Cytopathogenic Effect, Viral; D050091:Dendrimers / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry*; D004587:Electrophoresis, Agar Gel; D004797:Enzyme-Linked Immunosorbent Assay; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D018613:Microscopy, Confocal; D009841:Oligonucleotides / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology*; D011485:Protein Binding; D012709:Serum Albumin / Q000737:chemistry*; D012821:Silanes / Q000737:chemistry*; D012995:Solubility; D013873:Thionucleotides / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology*; D014162:Transfection; D014867:Water
D050091:Dendrimers; D004337:Drug Carriers; D009841:Oligonucleotides; D012709:Serum Albumin; D012821:Silanes; D013873:Thionucleotides; C504072:carbosilane; D014867:Water