Fabrication of Redox- and pH-Sensitive Self-Assembled Nano-Micelles with Pegylated β-Cyclodextrin for Codelivery of Doxorubicin and Cyclopalladated Ferrocene

We report a dual-responsive, self-assembled nano micelle for co-delivery of doxorubicin (DOX) and a previously reported cyclopalladated anti-cancer agent (CP). In this micelle system, doxorubicin and CP were electrostatically complexed to form a hydrophobic core while a conjugation of polyethylene glycol and beta-cyclodextrin (CD) was designed to construct the hydrophilic out-layer and stabilize the micelle. The interaction between pegylated CD and DOX-CP composite was achieved via inclusion of ferrocene moiety by CD, which could be broken by stimulating ROS that is over-expressed in many cancer cell lines. Moreover, the DOX-CP adduct can be destabilized under an acidic environment that exists in most solid tumors, which can further disassemble the micelle and release the two drugs. The fabricated micelle was characterized by TEM, DLS and its stimulus-responsive characteristic were confirmed by drugrelease profile. The in vitro cellular cytotoxicity was also evaluated, which showed improved anti-cancer effect of drugloaded micelle compared to free drugs.