Hypoxia-Triggered Singlet Oxygen and Nitrogen Mustard Release Towards a Synergistic Therapeutic Action

Abstract

We report an endoperoxide and nitrogen mustard conjugate (Pyd-endo) as a prodrug which can release cytotoxic singlet oxygen and aromatic nitrogen mustard under hypoxic conditions. Cell culture experiments demonstrated the hypoxia-responsiveness of prodrug and its ability to kill and inhibit the migration and proliferation of various types of cancer cells. Studies using tumor-bearing mice also and a liposomal formulation demonstrated its anticancer utility in vivo. Our design, not only addresses the challenges of tumor hypoxia and limited light penetration issues of PDT, but also present the power of combined cytotoxic action of singlet oxygen and a chemotherapy agent