Reactive oxygen species (ROS) are a collective term of small, highly reactive oxygen-derived species and radicals, including superoxide anion, hydrogen peroxide and hydroxyl radical and play essential roles in living organisms. However, its overproduction induces oxidative damages to biological molecules in cells, leading to cell death. Cancer cells, compared to normal cells, are under oxidative stress associated with an elevated level of ROS and are more vulnerable to oxidative stress induced by ROS generating agents. Thus, manipulation of the ROS level provides a logical approach to kill cancer cells preferentially, without significant toxicity to normal cells and great efforts have been dedicated to the development of strategies to induce cytotoxic oxidative stress for cancer treatment. Fenton reaction is an important biological reaction in which irons convert hydrogen peroxide to highly toxic hydroxyl radicals that escalate ROS stress. We developed Fenton reaction-performing polymer (PolyCAFe) micelles as a new class of ROS-manipulating anticancer therapeutic agents. Amphiphilic PolyCAFe was designed to incorporate H2O2-generating benzoyloxycinnamaldehyde and ferrocene in its backbone and self-assembles to form micelles that serve as Nano-Fenton reactors to generate highly cytotoxic hydroxyl radicals, killing cancer cells preferentially. PolyCAFe micelles could accumulate in tumors preferentially to remarkably suppress tumor growth, without toxicity to normal tissues. The Nano Fenton reactors could also kill bacteria in P. aeruginosa-infected mice and significantly increased the survival rate. This study demonstrates tremendous translatable potential of Nano-Fenton reactors as a new class of anticancer and antibacterial agent.

pH-responsive Fenton reaction performing polymeric micelles: Applications in anticancer and antibacterial therapy

253rd National Meeting (2017)

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