Poly(L-lysine)-based cylindrical copolypeptide brushes as potential drug and gene carriers

Cylindrical copolypeptide brush PLLF-g-(PLF-b-PLL), consisting of a poly(L-lysine-co-L-phenylalanine) (PLLF) backbone and poly(L-phenylalanine)-b-poly(L-lysine) (PLF-b-PLL) amphiphilic block copolypeptide side chains, has been synthesized, characterized, and evaluated as drug and gene carriers. PLLF-g-(PLF-b-PLL) brushes were synthesized by the multi-step ring-opening polymerization of amino acid N-carboxyanhydrides via a “grafting from” strategy. Transmission electron microscopy measurements and pyrene probe fluorescence study revealed that the synthesized copolypeptide brushes adopted nanosized cylindrical morphologies which resembled unimolecular polymeric micelles with a hydrophobic PLF core and a hydrophilic PLL periphery. An encapsulation study demonstrated that hydrophobic molecules (e.g., pyrene and oil red O) can be solubilized in the core of the copolypeptide brushes, while anionic hydrophilic molecules (e.g., rose bengal and methyl orange) can be entrapped into the brush periphery. Hydrophobic molecules and hydrophilic guests can be encapsulated simultaneously in a site-isolated state. Furthermore, the in vitro gene transfection efficiencies of copolypeptide brushes were evaluated in HEK293 and HeLa cells. The synthesized copolypeptide brushes exhibited low cytotoxicity and mediated efficient gene transfection. Our research suggested that these cylindrical copolypeptide brushes with a brush-like PLL periphery could be used as promising carriers for the codelivery of drugs and genes.