Abstract
Redox-responsive ferrocene (Fc)-grafted supramolecular block copolymers functionalized with hyaluronic acid (HA-g-β-CD/Fc-polymers or HAP) or folic acid (FA-g-β-CD/Fc-polymers or FAP) were synthesized by host-guest interaction. The copolymer structures were characterized by Fourier transform infrared spectroscopy, nuclear magnetic resonance, and gel permeation chromatography. The block copolymers self-assemble into spherical micellar aggregates in aqueous solution, and exhibit reversible redox characteristics in the presence of an oxidant and reductant. The tunable redox response was evaluated by transmission electron microscopy, ultraviolet-visible spectroscopy, cyclic voltammetry and dynamic light scattering. The micelles rapidly release DOX under oxidative and acidic condition in vitro. Furthermore, presence of HA and FA on the micelles enabled effective uptake by the CD44 and FA receptor-overexpressing cancer cells. Taken together, the redox responsive Fc-block copolymer micelles have good biocompatibility, biodegradability, low toxicity, and high selectivity, and are a highly promising drug delivery system for cancer therapy.
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