Benito, J.M. (Juan M.)
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- Trehalose-based siamese twin amphiphiles with tunable self-assembling, DNA nanocomplexing and gene delivery properties(Royal Society of Chemistry, 2019) Tros-de-Ilarduya, C. (Conchita); Ortiz-Mellet, C. (Carmen); Rodríguez-Lavado, J. (Julio); Carbajo-Gordillo, A.I. (Ana I.); García-Fernández, J.M. (José M.); Jiménez-Blanco, J.L. (José Luis); Di-Giorgio, C. (Christophe); Vélaz-Rivas, I. (Icíar); Benito, J.M. (Juan M.)An original family of multivalent vectors encompassing gemini and facial amphiphilicity, namely cationic Siamese twin surfactants, has been prepared fromthe disaccharide trehalose; molecular engineering lets us modulate the self-assembling properties and the topology of the nanocomplexes with plasmid DNA for efficient gene delivery in vitro and in vivo.
- Trifaceted Mickey Mouse amphiphiles for programmable self-assembly, DNA complexation and organ-selective gene delivery(European Chemical Societies Publishing, 2021) Carbajo-Gordillo, A.I. (Ana I.); González-Cuesta, M. (Manuel); Jiménez-Blanco, J.L. (José Luis); Benito, J.M. (Juan M.); Santana-Armas, M.L. (María L.); Carmona, T. (Thais); Di-Giorgio, C. (Christophe); Przybylski, C. (Cédric); Ortiz-Mellet, C. (Carmen); Tros-de-Ilarduya, C. (Conchita); Mendicuti, F. (Francisco); García-Fernández, J.M. (José M.)Instilling segregated cationic and lipophilic domains with an angular disposition in a trehalose-based trifaceted macrocyclic scaffold allows engineering patchy molecular nanoparticles leveraging directional interactions that emulate those controlling self-assembling processes in viral capsids. The resulting trilobular amphiphilic derivatives, featuring a Mickey Mouse architecture, can electrostatically interact with plasmid DNA (pDNA) and further engage in hydrophobic contacts to promote condensation into transfectious nanocomplexes. Notably, the topology and internal structure of the cyclooligosaccharide/pDNA co-assemblies can be molded by fine-tuning the valency and characteristics of the cationic and lipophilic patches, which strongly impacts the transfection efficacy in vitro and in vivo. Outstanding organ selectivities can then be programmed with no need of incorporating a biorecognizable motif in the formulation. The results provide a versatile strategy for the construction of fully synthetic and perfectly monodisperse nonviral gene delivery systems uniquely suited for optimization schemes by making cyclooligosaccharide patchiness the focus.