Combinational
therapy is a new trend in medical sciences to achieve a maximum therapeutic response of the drugs with a comparatively low incidence of severe adverse effects. To overcome the challenges of conventional formulations for
cancer chemotherapy, a
polymer-based complex nanomicellar system, namely CPM-DD, was developed co-delivering the anti-
cancer agent
doxorubicin (DOX) and potent
antioxidant dimethoxycurcumin (DiMC). The optimal mass ratio of DOX/DiMC in CPM-DD was determined as 1:6 due to the synergistic antiproliferative effect from in vitro cytotoxicity assay, while the biocompatible diblock copolymer of mPEG2000-PLA5000 was selected for
drug entrapment at an optimal feeding ratio of 9:1 to both drugs together. The uniform particles of CPM-DD with suitable particle size (∼30 nm) and stable
drug loading content (>9%) could be reliably obtained by self-assembly with the encapsulation yield up to 95%. Molecular dynamics simulation revealed the interaction mechanism responsible for forming these complex nanomicelles. The
acid-base interaction between two drugs would significantly improve their binding with the copolymer, thus leading to good colloidal stability and controlled drug release characteristics of CPM-DD. Systematic evaluation based on the MCF-7
breast tumor-bearing nude mice model further demonstrated the characteristics of tissue biodistribution of both drugs delivered by CPM-DD, which were closely related to the
drug loading pattern and greatly responsible for the improved anti-
cancer potency and attenuated toxicity of this complex formulation. Therefore, all the findings indicated that CPM-DD would be a good alternative to the conventional formulations of DOX and worthy of clinical application for
cancer chemotherapy.