4 years ago

A Combination of Guanidyl and Phenyl Groups on a Dendrimer Enables Efficient siRNA and DNA Delivery

A Combination of Guanidyl and Phenyl Groups on a Dendrimer Enables Efficient siRNA and DNA Delivery
Hong Chang, Hui Wang, Jia Zhang, Yiyun Cheng, Jia Lv
Gene therapy has received considerable attention due to its great potential in the treatment of various diseases; however, the design of efficient and biocompatible carriers for the delivery of siRNA as well as DNA still remains a major challenge. In this study, we developed an efficient carrier for gene delivery by modification of a compound containing both guanidyl and phenyl groups on the surface of a cationic dendrimer. The guanidyl group on the dendrimer facilitates nucleic acid condensation via specific guanidinium–phosphate interactions, whereas the phenyl group on the polymer is critical for efficient endosomal escape. The combination of guanidyl and phenyl shows a synergistic effect in facilitated endocytosis. The designed material is much more efficient in siRNA and DNA delivery than control materials such as dendrimers engineered with a guanidyl or phenyl group only, as well as intact dendrimers, and shows comparable efficacy to commercial transfection reagent Lipofectamine 2000. In addition, the material and its complex with nucleic acid show minimal toxicity on the transfected cells. This study provides a new strategy to develop multifunctional polymers for efficient siRNA and DNA delivery.

Publisher URL: http://dx.doi.org/10.1021/acs.biomac.7b00567

DOI: 10.1021/acs.biomac.7b00567

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