Amphiphilic Cationic Carbosilane–PEG Dendrimers: Synthesis and Applications in Gene Therapy

•Cationic Janus-type dendrimers with PEG and carbosilane moieties.•The amphiphilic dendrimers have been studied as vectors for gene therapy against HIV.•Amphiphilic dendrimers improves results with respect to homocarbosilane dendrimer.

Here we synthesized carbosilane, generation 1 to 3, and PEG-based dendrons functionalized at the periphery with NHBoc groups and at the focal point with azide and alkyne moieties, respectively. The coupling of these two types of dendrons via click chemistry led to the formation of new hybrid dendrimers with two distinct moieties, the hydrophobic carbosilane and the hydrophilic PEG-based dendron. The protected dendrimers were transformed into cationic ammonium dendrimers. These unique amphiphilic dendrimers were studied as vectors for gene therapy against HIV in peripheral blood mononuclear cells (PBMC) and their performance was compared with that of a PEG-free carbosilane dendrimer. The presence of the PEG moiety afforded lower toxicities and evidenced a weaker interaction between dendrimers and siRNA when compared to the homodendrimer analogous. Both features, lower toxicity and lower dendriplex strength, are key properties for use of these vectors as carriers of nucleic material.

Graphical abstractCationic ammonium Janus-type dendrimers have been synthesized via click chemistry coupling of carbosilane (generation 1–3) and PEG-based dendrons functionalized at the focal point with azide and alkyne moieties, respectively. These amphiphilic dendrimers have been studied as vectors for gene therapy against HIV in peripheral blood mononuclear cells (PBMC) and the results have been compared with a homocarbosilane dendrimer, observing the positive influence of the PEG unit.Figure optionsDownload full-size imageDownload as PowerPoint slide