Molecular Design of Dual Redox-Active Phospholipid Polymers with a Potent Anticancer Activity

Abstract

Redox-active compounds that disrupt the intracellular redox balance are promising anticancer agents because of the vulnerability of cancer cells to oxidative stress. The conjugation of different redox-active molecules can effectively achieve high therapeutic efficacy but can also lead to challenges owing to their typically poor water solubility and complicated organic synthesis. In this study, we designed a water-soluble, cell-penetrating, dual redox-active polymer (pMBFcAq) containing ferrocene (Fc) and anthraquinone (Aq) units. pMBFcAq retained the redox activity originating from the Fc and Aq units and induced oxidative stress and cell death more strongly against mouse colon cancer CT26 cells than polymers containing either Aq or Fc units alone. The in vitro anticancer activity of pMBFcAq was enhanced by adjusting its composition. Moreover, pMBFcAq significantly suppressed the in vivo growth of CT26 tumors, indicating potent anticancer activity. This study provides a strategy for the development of redox-active polymers with high therapeutic efficacy.