Highly branched poly(β-amino ester) polymers are developed to carry a gene and to enter cells for the production of protein.

1A series of hyperbranched poly(β-amino ester) polymers have been synthesized via a Michael addition approach for the fabrication of hydrogels for wound healing.

Highly branched poly(β-amino esters) (HPAEs) are developed via a facile and controllable "A2+B3/B2" strategy successfully. As nonviral gene delivery vectors, the performance of HPAEs is superior to the well-studied linear counterpart as well as the leading commercial reagent Superfect. When combined with minicircle DNA construct, HPAEs can achieve ultrahigh gene transfection efficiency, especially in keratinocytes.

No abstract

A successful polymeric gene delivery vector is denoted by both transfection efficiency and biocompatibility. However, the existing vectors with combined high efficacy and minimal toxicity still fall short. The most widely used polyethylene imine (PEI), polyamidoamine (PAMAM) and poly(dimethylaminoethyl methacrylate) (PDMAEMA) suffer from the correlation: either too toxic or little effective. Here, we demonstrate that with highly branched poly(β-amino esters) (HPAEs), a type of recently developed gene delivery vector, the high gene transfection efficiency and low cytotoxicity can be achieved simultaneously at high molecular weight (MW). The interactions of HPAE/DNA polyplexes with cell membrane account for the favorable correlation between molecular weight and biocompatibility. In addition to the effect of molecular weight, the molecular configuration of linear and branched segments in HPAEs is also pivotal to endow high transfection efficiency and low cytotoxicity. These findings provide renewed perspective for the further development of clinically viable gene delivery vectors.