Polypeptide–poly(ethylene glycol) miktoarm star copolymers with a fluorescently labeled core: synthesis, delivery and imaging of siRNA

Abstract

A facile synthetic pathway to polypeptide–PEG miktoarm star copolymers with a fluorescently labeled core has been developed by combination of the reversible addition-fragmentation chain transfer (RAFT) arm-first technique and an aldehyde–aminooxy click reaction. A star polymer backbone with a fluorescently labeled and aldehyde-functionalized core was prepared via the cross-linking of a PEG macro-RAFT agent using an aldehyde-bearing divinyl monomer, 6,6′-(ethane-1,2-diylbis(oxy))bis(3-vinylbenzaldehyde), in combination with a fluorescent aluminum tris(8-hydroxyquinoline)-bearing cross-linker. The aldehyde groups on the core were then coupled with the newly designed aminooxy terminated poly(γ-benzyl-L-glutamate) (PBLG-ONH₂) to generate the fluorescently labeled PBLG–PEG miktoarm star copolymer. Further aminolysis of the benzyl groups of PBLG arms with β-hydroxyethylenediamine endowed the miktoarm star polymer with the ability to capture negatively charged siRNA via electrostatic interactions. Owing to the biocompatible polypeptide and PEG arms, the obtained miktoarm star polymer exhibited low cytotoxicity. The miktoarm star polymer/siRNA complexes (formed at N/P ratio = 16) showed a relatively small particle size and appropriate positive zeta potentials, facilitating the cellular uptake. Besides, with its fluorescent property, the star polymer could serve as a probe for cellular tracing. This multifunctional star polymer would thus be of particular interest because of its promising potential in, for example, simultaneous gene delivery and bioimaging.