Co-delivery of daunomycin and oxaliplatin by biodegradable polymers for safer and more efficacious combination therapy

A new hydrophilic pro-drug, Oxa(IV)-COOH, was prepared and attached to a biodegradable amphiphilic polymer to form polymer-Oxa(IV) conjugate. Then it was co-assembled with polymer-danuorubicin (polymer-DRB) conjugates to mixed micelles(M(DRB/Oxa(IV)). In this way, both DRB and Oxa(IV) complex will be located in the core part of the micelles and get effectively protected. Once they enter the cancerous cells, due to the drastic drop in pH and increase in the concentration of reducing agent such as GSH and ascorbic acid, both DRB and active platinum(II) species will be released from the micelles by hydrolysis and reduction respectively. Then, the released DRB undergo further insertion into the DNA strand and Pt drugs go to cross‐link with DNA respectively. In this way, they were combined to promote cell to death more effectively. Because DRB and Oxa(IV) complex are attached to different polymer chains, their relative doses can be adjusted easily. Furthermore, synergetic effect of the composite micelles proved to be realized in vitro and in vivo. Safer and more efficacious combination therapy can be realized with this strategy.120