Nano-Fenton Reactors as a New Class of Oxidative Stress Amplifying Anticancer Therapeutic Agents

• DOI: 10.1021/acsami.5b12523
• Publication Date: 2016-02-18T11:54:33Z
• Authors: Byeongsu Kwon; Eunji Han; Wonseok Yang; Wooram Cho; Wooyoung Yoo; Junyeon Hwang; Byoung-Mog Kwon; Dongwon Lee
• Keywords: Hydroxyl Radical; Metallocenes; Polymers; Iron; Mice, Nude; Antineoplastic Agents; Apoptosis; DNA Fragmentation; Hydrogen Peroxide; Hydrogen-Ion Concentration; 01 natural sciences; 0104 chemical sciences; 3. Good health; Mice; Oxidative Stress; HEK293 Cells; Cell Line, Tumor; Neoplasms; NIH 3T3 Cells; Animals; Humans; Ferrous Compounds; Micelles

Cancer cells, compared to normal cells, are under oxidative stress associated with an elevated level of reactive oxygen species (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 (H2O2) to highly toxic hydroxyl radicals that escalate ROS stress. Here, we report Fenton reaction-performing polymer (PolyCAFe) micelles as a new class of ROS-manipulating anticancer therapeutic agents. Amphiphilic PolyCAFe incorporates H2O2-generating benzoyloxycinnamaldehyde and iron-containing compounds in its backbone and self-assembles to form micelles that serve as Nano-Fenton reactors to generate cytotoxic hydroxyl radicals, killing cancer cells preferentially. When intravenously injected, PolyCAFe micelles could accumulate in tumors preferentially to remarkably suppress tumor growth, without toxicity to normal tissues. This study demonstrates the tremendous translatable potential of Nano-Fenton reactors as a new class of anticancer drugs.