Theranostics 2013; 3(2):116-126. doi:10.7150/thno.5411

Research Paper

Superparamagnetic Iron Oxide Nanoparticles: Amplifying ROS Stress to Improve Anticancer Drug Efficacy

Gang Huang1*, Huabing Chen1*, Ying Dong1*, Xiuquan Luo1,2, Haijun Yu1, Zachary Moore1,2, Erik A. Bey1,2, David A. Boothman1,2✉, Jinming Gao1✉

1. Departments of Pharmacology, Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390-8807, USA;
2. Radiation Oncology, Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390-8807, USA.
*Authors contributed equally to this work.

Abstract

Superparamagnetic iron oxide nanoparticles (SPION) are an important and versatile nano- platform with broad biological applications. Despite extensive studies, the biological and pharmacological activities of SPION have not been exploited in therapeutic applications. Recently, β-lapachone (β-lap), a novel anticancer drug, has shown considerable cancer specificity by selectively increasing reactive oxygen species (ROS) stress in cancer cells. In this study, we report that pH-responsive SPION-micelles can synergize with β-lap for improved cancer therapy. These SPION-micelles selectively release iron ions inside cancer cells, which interact with hydrogen peroxide (H2O2) generated from β-lap in a tumor-specific, NQO1-dependent manner. Through Fenton reactions, these iron ions escalate the ROS stress in β-lap-exposed cancer cells, thereby greatly enhancing the therapeutic index of β-lap. More specifically, a 10-fold increase in ROS stress was detected in β-lap-exposed cells pretreated with SPION-micelles over those treated with β-lap alone, which also correlates with significantly increased cell death. Catalase treatment of cells or administration of an iron chelator can block the therapeutic synergy. Our data suggest that incorporation of SPION-micelles with ROS-generating drugs can potentially improve drug efficacy during cancer treatment, thereby provides a synergistic strategy to integrate imaging and therapeutic functions in the development of theranostic nanomedicine.

Keywords: superparamagnetic iron oxide nanoparticles, β-lapachone, reactive oxygen species, Fenton reaction, theranostic nanomedicine.

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How to cite this article:
Huang G, Chen H, Dong Y, Luo X, Yu H, Moore Z, Bey EA, Boothman DA, Gao J. Superparamagnetic Iron Oxide Nanoparticles: Amplifying ROS Stress to Improve Anticancer Drug Efficacy. Theranostics 2013; 3(2):116-126. doi:10.7150/thno.5411. Available from http://www.thno.org/v03p0116.htm