Facile synthesis of a multifunctional copolymer via a concurrent RAFT-enzymatic system for theranostic applications

Abstract

Facile preparation of well-defined and multifunctional polymers is of great importance for the development of polymer-based drug carriers. By performing enzymatic transacylation during RAFT polymerization, diverse monomers with different functions were generated in situ and simultaneously copolymerized via the RAFT process to form a well-defined multifunctional copolymer precursor which contains fluorine, polyethylene glycol (PEG), benzaldehyde and azido groups. The glucose moiety (which represents a possible targeting group for tumor treatment) was conjugated to this precursor via a copper-catalyzed azide alkyne cycloaddition (CuAAc) reaction to generate the polymer drug carrier. A ¹⁹F MRI phantom was performed for the polymer drug carrier, indicating its potential as a possible ¹⁹F MRI tracer. The polymer drug carrier has been shown to specifically bind to lectin due to the contained glucose moiety, demonstrating its potential targeting effect. Then, doxorubicin (dox, an anticancer drug) was conjugated with the polymer drug carrier through imine chemistry to generate a target polymer–dox complex. This polymer–dox complex possesses amphiphilic character and self-assembles in aqueous solution into spherical micelles with a size of ∼30 nm, which exhibit much faster release of dox at pH 5.5 than at pH 7.4. Subsequent cell experiments showed that the polymer–dox complex is less toxic than native dox to normal cells while retaining similar cytotoxicity against cancer cells, suggesting that the polymer drug carrier is potentially a safe and effective drug delivery system. We believe that as several reactive moieties can be implanted into the polymer structure in a one-pot manner to achieve a multifunctional polymer precursor for efficient post-modification, this concurrent tandem polymerization (CTP) system might be useful for the development of novel anticancer theranostic nanomedicines.