Development of functional amino acid-based star polymers

Abstract

Highly functionalized core cross-linked star (CCS) polymers composed entirely of naturally-occurring amino acids were prepared via the sequential ring-opening polymerisation (ROP) of amino acidN-carboxyanhydride (NCA) derivatives in a facile one-pot, arm-first strategy. The formation of the star polymers was investigated using side-chain protected poly(ε-Z-L-lysine) (PZLL) and poly(γ-benzyl-L-glutamic acid) (PBGA) macroinitiators with various molecular weights in combination with a cystine NCA cross-linker to afford poly(ε-Z-L-lysine)_armspoly(L-cystine)_core (PZLL_armsPLC_core) and poly(γ-benzyl-L-glutamic acid)_armspoly(L-cystine)_core (PBLG_armsPLC_core) stars, respectively. As the cross-linker to macroinitiator ratio or macroinitiator molecular weights were increased the molecular weights, average number of arms and core size of the resulting stars also increased. Core-isolated NCA moieties remaining after star formation provided a facile approach to core-functionalization with primary amines bearing different functionalities, including aminomethyl pyrene, propargylamine and hexylamine. UV-vis spectroscopic analysis of PZLL_armsPLC_core and PBLG_armsPLC_core stars core-functionalised with aminomethyl pyrene provided high loadings of 240 and 128 mol/mol stars, respectively. Furthermore, stars with alkyne functionalized cores were capable of undergoing further click reactions with azido derivatives, demonstrating the accessibility of the core-isolated moieties. Deprotection of the PZLL_armsPLC_core and PBLG_armsPLC_core stars yielded water soluble CCS polymers with poly(L-lysine) and poly(L-glutamic acid) arms, respectively, and functionalised cores. In addition, direct hydrazinolysis of the PBLG_armsPLC_core star provided hydrazide functionalities along the arms, which allow for conjugation of drug molecules via pH sensitive hydrazone linkers. These results open up exciting opportunities for the development of star polymerdrug delivery systems, whereby a lack of functionality, biocompatibility and biodegradability are often limiting factors.