Star-shaped poly(l-lysine) with polyester bis-MPA dendritic core as potential degradable nano vectors for gene delivery

Cationic star-shaped poly(L-lysine) are efficient nanovectors for the delivery of nucleic acids (gene delivery). They are commonly obtained by the ring-opening polymerisation of L-lysine N-carboxyanhydrides (NCA) from multifunctional amine initiators such as dendrimers. To date, commonly reported dendritic precursors are non-degradable which can cause dose dependant cytotoxicity in vivo. Herein, we present a new synthetic route for the preparation of star-shaped poly(L-lysine) from ammonium terminated 2,2-bis-(hydroxymethyl)propionic acid (bis-MPA) dendrimers. A range of well-defined star polypeptides with exceptionally low dispersities (ĐM < 1.05) was obtained by varying the dendrimer generation and adjusting the monomer to initiator feed ratio. The ability of efficient dendrimer core degradation was confirmed under physiological and basic conditions. Moreover, preliminary pDNA complexation studies demonstrate successful polyplex formation between the gene cargo and the star poly(L-lysine). The results suggest that the bis-MPA star poly(L-lysine) platform is a promising fully degradable alternative to leading non-degradable polymeric vectors.