Synthesis of polycation dendrimers for gene delivery

Description

Gene therapy requires the delivering of genetic materials to the interior of a target cell through specific vectors which can be viral or nonviral. Nonviral synthetic vectors are considered a very promising, safer alternative to the viral ones which are used at present in the majority of clinics, but suffer from drawbacks such as immune response, recombination of viruses, limitation of the size of the genetic material to be internalized. Synthetic nonviral vectors are cationic lipids or polymers able to electrostatically bind the negative charged genetic material to form nanostructured complexes smaller than 100 nm. In this field we turned our attention to dendrimers, for their well-defined nano-structured architecture, high symmetry, narrow polydispersity and possible introduction of selected different functional groups at the periphery. Polyester-based dendrimers bearing hydroxy end-groups derived from 2,2-bis(hydroxy-methyl)propanoic acid appeared to us particularly attractive due to their low toxicity in vivo and possibility of functionalization. In this communication we report the synthesis of dendrimers developed to the fifth generation, their functionalization with proper amino acids forming polycationic systems able to bind genetic material, and their NMR characterization. A relevant synthetic work concerns the not simple introduction on the dendrimers surface of arginine moieties, whose interest is enhanced by the fact that residues of the guanidine-type can favor the internalization of synthetic polymers into cells.

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