Amphiphilic Cylindrical Copolypeptide Brushes: Synthesis, Characterization And Properties

The research mainly aimed to synthesize a series of amphiphilic cylindrical copolypeptide brushes as potential drug delivery carriers, and to investigate their capacities to encapsulate hydrophobic and cationic hydrophilic model compounds. Cylindrical copolypeptide brushes PLLF-g-(PLF-b-PLG) consisted of poly(L-lysine-co-L-phenylalanine) (PLLF) as the backbone and poly(L-phenylalanine)-b-poly(L-glutamic acid) (PLF-b-PLG) as side chains, and their syntheses were carried out via"grafting from"strategy as follows: (1) L-phenylanaline (Phe),γ-benzyl-L-glutamate (BLG), orε-benzyoxycarbonyl-L-lysine (ZLL) was reacted with triphosgene to generate the corresponding amino acid N-carboxylanhydrides (NCAs): Phe-NCA, BLG-NCA, or ZLL-NCA, respectively; (2) the terminal amine group of n-hexylamine was used to initiate the ring-opening polymerization of Phe-NCA and ZLL-NCA mixture to prepare a linear random copolypeptide poly(ε-benzyoxycarbonyl-L-lysine-co-L-phenylalanine) (PZLLF), poly(L-lysine-co-L-phenylalanine) (PLLF) was then obtained after the depeorection of benzyl groups in trifluoroacetic acid in the presence of HBr; (3) the pedent amine groups of PLLF were used to initiate the sequential ring-opening polymerization of Phe-NCA and BLG-NCA, resulting in cylindrical molecular brushes PLLF-g-(PLF-b-PBLG) with a PLLF backbone and poly(L-phenylalanine)-b-poly(γ-benzyl-L-glutamate) (PLF-b-PBLG) side chains; (4) the side chains of PBLG were removed by HBr in dichloroacetic acid to generate the final amphiphilic cylindrical brushes PLLF-g-(PLF-b-PLG). The synthesized copolypeptide brushes were characterized by 1H NMR, gel permeation chromatography (GPC), and transmission electron microscope (TEM). In aqueous solution, the copolypeptide brush adopted a worm-like cylindrical morphology with a length about 100 nm and a width around 20 nm. Under physiological pH, the synthesized cylindrical copolypeptide brushes resembled unimolecular polymeric micelles with a poly(L-phenylalanine) hydrophobic core and a poly(L-glutamate) hydrophilic shell. The encapsulation capacity of these polypeptide brushes were evaluated using pyrene and oil red O as model hydrophoic compunds as well as crystal violet and doxorubicin hydrochloride as model cationic hydrophilic compounds. The encapsulation study demonstrated that these water-soluble, biodegradable copolypeptide brushes encapsulated hydrophobic compounds and cationic hydrophilic guest molecules simultaneously.