Micelles of ferrocene/aldehyde-containing triblock polynorbornene: Preparation, biocompatibility, dual-cargo-loading and oxidation/pH-sensitive release behavior

Abstract Using the ring-opening metathesis polymerization, a new amphipathic triblock polynorbornene-based copolymer containing reactive aldehyde, redox-active ferrocene, and dendritic oligoethylene glycols units (PNCHO-PNFc-PNTEG), was controllably synthesized and exhibited the dual-cargo loading capacity with the oxidation/pH stimuli-responsive behavior. PNCHO-PNFc-PNTEG could conjugate the amino-containing doxorubicin (DOX) by the acid-sensitive Schiff base reaction. The DOX-grafted PNCHO-PNFc-PNTEG could further self-assemble into spherical nanoscale polymeric micelles that can encapsulate the second model cargo rhodamine B (RhB). The step-by-step release behavior of the loaded two cargos was observed. Namely, the loaded RhB could be firstly released under the stimulus of oxidant, and the grafted DOX could be then released under acidic condition. Moreover, PNCHO-PNFc-PNTEG micelles showed excellent biocompatibility both in in vitro L929 cell test and in vivo zebrafish embryo toxicity experiments. Thus, PNCHO-PNFc-PNTEG as polymeric carrier has great application potential in the medical field for controllable drug release.