title: Superparamagnetic iron oxide nanoparticles: amplifying ROS stress to improve anticancer drug efficacy.
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 (H(2)O(2)) 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.
authors: Departments of Pharmacology, Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390-8807, USA.
authors: Gang
authors: G
authors: Huang
authors: Huabing
authors: H
authors: Chen
authors: Ying
authors: Y
authors: Dong
authors: Xiuquan
authors: X
authors: Luo
authors: Haijun
authors: H
authors: Yu
authors: Zachary
authors: Z
authors: Moore
authors: Erik A
authors: EA
authors: Bey
authors: David A
authors: DA
authors: Boothman
authors: Jinming
authors: J
authors: Gao
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D004847:Epithelial Cells / Q000187:drug effects; D005290:Ferric Compounds / Q000627:therapeutic use*; D006801:Humans; D008280:Magnetics; D057054:Molecular Imaging / Q000379:methods; D058990:Molecular Targeted Therapy / Q000379:methods*; D050997:Nanomedicine / Q000379:methods; D053758:Nanoparticles / Q000627:therapeutic use*; D009285:Naphthoquinones / Q000627:therapeutic use*; D016877:Oxidants / Q000627:therapeutic use*; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D005290:Ferric Compounds; D009285:Naphthoquinones; D016877:Oxidants; D017382:Reactive Oxygen Species; C000499:ferric oxide; C014638:beta-lapachone
keywords: Fenton reaction; reactive oxygen species; superparamagnetic iron oxide nanoparticles; theranostic nanomedicine.; β-lapachone