title: Novel 'Si-C' carbosilane dendrimers as carriers for anti-HIV nucleic acids: studies on complexation and interaction with blood cells.
abstract: Treatment of HIV infection by gene therapy is a promising tool for combating AIDS. One of the primary limitations of gene therapy is the effective delivery of nucleic acids to the target cells. Dendrimers are nanoparticles that are increasingly being used as nucleic acid vehicles. We have synthesized "Si-C" amino-terminated carbosilane dendrimers [GnO3(NMe3)m](m+) functionalized with quaternary ammonium (NMe3(+)) terminal groups via hydrosilylation of allyl dimethylamine with the corresponding GnO3(SiH)m dendrimers and further addition of MeI. These dendrimers are soluble in water. Initially, complexation between these "Si-C" dendrimers and anti-HIV nucleic acids (oligodeoxynucleotides ANTITAR and GEM91, siRNA siP24) was studied and molar ratios for complete complexation were determined. Then the charge and size of the dendriplexes (complexes of "Si-C" dendrimers with nucleic acids) were analyzed and it was found that they possessed charges of +5 to +40 mV and sizes of 60-600 nm (zeta-size) or 50-100 nm (atomic force microscopy) suitable for cell transfection. Stability studies showed that the dendriplexes were stable over time and were resistant to degradation by serum albumin. The effects of dendrimers and their dendriplexes on erythrocytes (isolated and in whole blood) revealed that the dendriplexes were significantly less cytotoxic than the pure dendrimers. The effects of dendrimers and their dendriplexes on peripheral blood mononuclear cells (the main target of HIV) were analyzed and it was found that the dendriplexes were 10 times less cytotoxic than the pure dendrimers. Finally, transfection experiments revealed that "Si-C"-carbosilane dendrimers had a restricted ability to deliver long-chain double-stranded nucleic acids. The results indicate that these cationic carbosilane dendrimers are good candidates for delivering short-chain siRNA and oligodeoxynucleotide to HIV-infected peripheral blood mononuclear cells or lymphocytes.
authors: Department of General Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, Lodz, Poland. epedz@biol.uni.lodz.pl
authors: Elzbieta
authors: E
authors: Pedziwiatr-Werbicka
authors: Elena
authors: E
authors: Fuentes
authors: Volha
authors: V
authors: Dzmitruk
authors: Javier
authors: J
authors: Sánchez-Nieves
authors: Marharyta
authors: M
authors: Sudas
authors: Elizaveta
authors: E
authors: Drozd
authors: Antos
authors: A
authors: Shakhbazau
authors: Dzmitry
authors: D
authors: Shcharbin
authors: Francisco Javier
authors: FJ
authors: de la Mata
authors: Rafael
authors: R
authors: Gomez-Ramirez
authors: Maria Angeles
authors: MA
authors: Munoz-Fernandez
authors: Maria
authors: M
authors: Bryszewska
mesh_terms: D019380:Anti-HIV Agents / Q000737:chemistry*; D002470:Cell Survival; D050091:Dendrimers / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D015316:Genetic Therapy; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000737:chemistry / Q000187:drug effects* / Q000821:virology; D008214:Lymphocytes / Q000737:chemistry / Q000187:drug effects / Q000821:virology; D009696:Nucleic Acids / Q000737:chemistry*; D010316:Particle Size; D012821:Silanes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D055672:Static Electricity; D013329:Structure-Activity Relationship; D013499:Surface Properties
chemical_list: D019380:Anti-HIV Agents; D050091:Dendrimers; D004337:Drug Carriers; D009696:Nucleic Acids; D012821:Silanes; C504072:carbosilane