Synthesis of well-defined chitosan-based tricomponent copolymers for constructing multifunctional delivery systems

Abstract

Chitosan-based tricomponent copolymers, chitosan-g-poly(e-caprolactone)-(g-poly(oligo(ethylene glycol) methacrylate)) (CS-PCL-POEGMA, CPP), are synthesized as multifunctional nanocarriers for antitumor therapy. 2-Bromoisobutyric acid and PCL are first site-specifically conjugated onto the hydroxy groups of chitosan backbone through conventional coupling chemistry to give CS-PCL-Br using sodium dodecyl sulfate–chitosan complex as an organosoluble intermediate. CPP-PCL-Br is further used for initiating the single electron transfer-living radical polymerization of OEGMA in the mixed solvent of dimethyl sulfoxide and lactic acid, yielding CPP. One-pot reaction of CPP with a small amount of NaN3 under the catalysis of Cu(I)Br/tris-(2-dimethylaminoethyl)amine converts the bromo ends of POEGMA grafts to azide functionality, which is used for conjugation of folic acid targeting moiety via azide–alkyne click reactions. The resultant tricomponent copolymers can assemble into spherical micelles with the capacity of coincorporating indocyanine green and Doxorubicin through electrostatic and hydrophobic interactions, respectively. The dual-agent-loaded micelles display a combined effect for combating HepG2 cells when irradiated with near-infrared laser. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012