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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.

Current anti-HIV therapies are capable of controlling viral infection but do not represent a definitive cure. They rely on the administration of antiretroviral nucleoside analogues, either alone or in combination with vectors. Dendrimers are branched, synthetic polymers with layered architectures, promising non-viral vectors in gene therapy. The aim of the paper was to study the interactions between three anti-HIV antisense oligonucleotides (ODNs): SREV, ANTI TAR, GEM91 and different generation polypropylene imine dendrimers (PPI) by monitoring changes in the fluorescence polarization of fluorescein attached to the ends of the ODNs when increasing concentrations of dendrimers were added. Laser Doppler electrophoresis, dynamic light scattering (DLS) and transmission electron microscopy (TEM) were used to characterize, respectively, zeta potential, particle size and morphology of dendriplexes formed in different molar ratios. Antisense oligonucleotides interacted with polypropylene imine dendrimers in different molar ratios depending on generation. Zeta potential of dendriplexes varied from (−25 to −21) mV to −5 mV (for PPIG3 and PPIG4 complexes) and to zero (for PPIG2 complexes). The structures presented a polydisperse size from about 50 nm to even 700–800 nm by TEM and about 250 nm by DLS. It means that besides single dendriplexes, aggregates were also present.