초록 |
A bio-triggered drug delivery system of degradable core cross-linked (CCL) prodrug micelles was prepared by click chemistry. DOX conjugated block copolymers of azido functional poly(ethylene oxide)-b-poly(glycidyl methacrylate) were synthesized by the combination of RAFT polymerization, epoxide ring-opening reaction, and acid-cleavable hydrazone linkages. The CCL prodrug micelles were produced by the reaction of dipropargyl 3,3’-dithiodipropionate cross-linking agents with the azido groups of the micellar core via alkyne-azide click reaction, which were denoted as CCL/SS. The high DOX conjugation efficiency was 88.4%. In contrast to a very slow DOX release from CCL/SS prodrug micelles under the physiological condition (pH 7.4), the drug release is much faster (90%) at pH 5.0 and 10 mM of GSH after 96 h. The cytotoxicity test and confocal laser scanning microscopy analysis revealed that CCL/SS prodrug micelles had much enhanced intracellular drug release capability in HepG2 cells. |