Superparamagnetic iron oxide nanoparticles: Amplifying ros stress to improve anticancer drug efficacy

Gang Huang, Huabing Chen, Ying Dong, Xiuquan Luo, Haijun Yu, Zachary Moore, Erik A. Bey, David A. Boothman, Jinming Gao

Research output: Contribution to journalArticle

162 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)116-126
Number of pages11
JournalTheranostics
Volume3
Issue number2
DOIs
StatePublished - 2013

Fingerprint

Nanoparticles
Micelles
Reactive Oxygen Species
Pharmaceutical Preparations
Neoplasms
Iron
Therapeutics
Ions
Chelating Agents
ferric oxide
Catalase
Hydrogen Peroxide
Cell Death
Pharmacology

Keywords

  • β-lapachone
  • Fenton reaction
  • Reactive oxygen species
  • Superparamagnetic iron oxide nanoparticles
  • Theranostic nanomedicine

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Pharmacology, Toxicology and Pharmaceutics (miscellaneous)

Cite this

Superparamagnetic iron oxide nanoparticles : Amplifying ros stress to improve anticancer drug efficacy. / Huang, Gang; Chen, Huabing; Dong, Ying; Luo, Xiuquan; Yu, Haijun; Moore, Zachary; Bey, Erik A.; Boothman, David A.; Gao, Jinming.

In: Theranostics, Vol. 3, No. 2, 2013, p. 116-126.

Research output: Contribution to journalArticle

Huang, Gang ; Chen, Huabing ; Dong, Ying ; Luo, Xiuquan ; Yu, Haijun ; Moore, Zachary ; Bey, Erik A. ; Boothman, David A. ; Gao, Jinming. / Superparamagnetic iron oxide nanoparticles : Amplifying ros stress to improve anticancer drug efficacy. In: Theranostics. 2013 ; Vol. 3, No. 2. pp. 116-126.
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