Toxic Reactive Oxygen Species Enhanced Synergistic Combination Therapy by Self-Assembled Metal-Phenolic Network Nanoparticles

Yunlu Dai; Zhen Yang; Siyuan Cheng; Zhongliang Wang; Ruili Zhang; Guizhi Zhu; Zhantong Wang; Bryant C Yung; Rui Tian; Orit Jacobson; Can Xu; Qianqian Ni; Jibin Song; Xiaolian Sun; Gang Niu; Xiaoyuan Chen

doi:10.1002/adma.201704877

Toxic Reactive Oxygen Species Enhanced Synergistic Combination Therapy by Self-Assembled Metal-Phenolic Network Nanoparticles

Adv Mater. 2018 Feb;30(8). doi: 10.1002/adma.201704877. Epub 2018 Jan 8.

Authors

Yunlu Dai^{1

2}, Zhen Yang², Siyuan Cheng², Zhongliang Wang¹, Ruili Zhang¹, Guizhi Zhu², Zhantong Wang², Bryant C Yung², Rui Tian², Orit Jacobson², Can Xu², Qianqian Ni², Jibin Song², Xiaolian Sun³, Gang Niu², Xiaoyuan Chen²

Affiliations

¹ Engineering Research Center of Molecular-imaging and Neuro-imaging of Ministry of Education, School of Life Science and Technology, Xidian University, Xi'an, Shaanxi, 710126, China.
² Laboratory of Molecular Imaging and Nanomedicine (LOMIN), National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH), Bethesda, MD, 20892, USA.
³ State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics & Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, 361005, China.

PMID: 29315862
DOI: 10.1002/adma.201704877

Abstract

Engineering functional nanomaterials with high therapeutic efficacy and minimum side effects has increasingly become a promising strategy for cancer treatment. Herein, a reactive oxygen species (ROS) enhanced combination chemotherapy platform is designed via a biocompatible metal-polyphenol networks self-assembly process by encapsulating doxorubicin (DOX) and platinum prodrugs in nanoparticles. Both DOX and platinum drugs can activate nicotinamide adenine dinucleotide phosphate oxidases, generating superoxide radicals (O₂^•- ). The superoxide dismutase-like activity of polyphenols can catalyze H₂ O₂ generation from O₂^•- . Finally, the highly toxic HO^• free radicals are generated by a Fenton reaction. The ROS HO^• can synergize the chemotherapy by a cascade of bioreactions. Positron emission tomography imaging of ⁸⁹ Zr-labeled as-prepared DOX@Pt prodrug Fe³⁺ nanoparticles (DPPF NPs) shows prolonged blood circulation and high tumor accumulation. Furthermore, the DPPF NPs can effectively inhibit tumor growth and reduce the side effects of anticancer drugs. This study establishes a novel ROS promoted synergistic nanomedicine platform for cancer therapy.

Keywords: combination therapy; metal-polyphenol networks; positron emission tomography; reactive oxygen species; self-assembly.