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

摘要

Chitosan-based tricomponent copolymers, chitosan-g-poly(ε- 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 NaN _3 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.