Polycationic adamantane-based dendrons form nanorods in complex with plasmid DNA

Abstract

Nonviral vectors such as cationic dendrimers and dendrons are demonstrating great properties for their use as gene delivery systems. A good carrier has to efficiently bind and protect the genetic material, but many of the newly developed vectors already fail at this initial step. A continuous and rational design of novel molecular structures is therefore beneficial to this field. Here we report the study of the complexation between different polycationic adamantane-based dendrons, called HYDRAmers, with a model plasmid DNA (pDNA). The role of the dendron generation, the cationic periphery and the functionalization at the focal point on the binding has been thoroughly evaluated. We discovered how appropriate chemical modifications could improve efficiently the complexation to get HYDRAplexes with very good pDNA binding and protecting properties. Despite these favorable characteristics, the unexpected morphology of the complexes forming long nanorods can explain the relatively low transfection performance. Both the reported literature data that guided us for the design of the HYDRAmers and the lessons learned from this work should broadly inform for future development of well-defined gene carriers. Our results also strongly encourage to proceed on the study of the polycationic adamantane-based dendrons for alternative therapies like gene silencing.