Low-intensity focused ultrasound-augmented Cascade chemodynamic therapy via boosting ROS generation

Liming Deng; Mingzhu Liu; Danli Sheng; Yuanli Luo; Dong Wang; Xian Yu; Zhigang Wang; Haitao Ran; Pan Li

doi:10.1016/j.biomaterials.2021.120710

Low-intensity focused ultrasound-augmented Cascade chemodynamic therapy via boosting ROS generation

Biomaterials. 2021 Apr:271:120710. doi: 10.1016/j.biomaterials.2021.120710. Epub 2021 Feb 9.

Authors

Liming Deng¹, Mingzhu Liu², Danli Sheng³, Yuanli Luo¹, Dong Wang⁴, Xian Yu⁵, Zhigang Wang¹, Haitao Ran¹, Pan Li⁶

Affiliations

¹ Institute of Ultrasound Imaging & Department of Ultrasound, The Second Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ultrasound Molecular Imaging, Chongqing, 400010, PR China.
² Institute of Ultrasound Imaging & Department of Ultrasound, The Second Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ultrasound Molecular Imaging, Chongqing, 400010, PR China; Department of Ultrasound, Maternal and Child Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430000, PR China.
³ Department of Ultrasound, Fudan University Shanghai Cancer Center, Shanghai, 200032, PR China.
⁴ Department of Ultrasound, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
⁵ Phase Ι Clinical Trial Center, The Second Affiliated Hospital of Chongqing Medical University, 400010, Chongqing, PR China.
⁶ Institute of Ultrasound Imaging & Department of Ultrasound, The Second Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ultrasound Molecular Imaging, Chongqing, 400010, PR China. Electronic address: lipan@hospital.cqmu.edu.cn.

PMID: 33610047
DOI: 10.1016/j.biomaterials.2021.120710

Abstract

Fenton reaction-mediated chemodynamic therapy (CDT), which destroys tumor cells by converting H₂O₂ into cytotoxic hydroxyl radical (OH) and singlet oxygen (¹O₂) species, is a promising field. However, Fenton-based CDT is severely impaired by the inappropriate tumor environment associated with undesirable intratumoral acidity and insufficient H₂O₂ supply in tumor microenvironment (TME). Therefore, a strategy that can address these concerns is highly desired and beneficial for boosting such treatment. Herein, a magnetic nanoreactor system (denoted as poly (lactic-co-glycolic acid) (PLGA)-superparamagnetic iron oxide (SPIO)&vitamin C (Vc) was constructed with Vc in the core, SPIO on the shell, and PLGA as the building carrier. Upon low-intensity focused ultrasound irradiation, on-demand Vc release can locally decompose into H₂O₂, which can generate a favorable condition for facilitating SPIO-based Fenton-like reaction and result in continuous O₂ and OH/¹O₂ generation. The TME modulation-augmented CDT by this nanoreactor based on the reinforced Fenton reaction tremendously improved the antitumor outcomes, especially under increased accumulation contributed by magnetic targeting combined with enhanced permeability and retention effect. Moreover, the explosive production of oxygen can be monitored by real-time photoacoustic imaging, offering a noninvasive means to forecast the treatment efficacy. Therefore, this established microenvironment modulation strategy for augmenting Fenton reaction-based CDT paves a new avenue to realize highly efficient cancer theranostics.

Keywords: Chemodynamic therapy; Fenton reaction; Low-intensity focused ultrasound; Real-time monitoring; Vitamin C.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cell Line, Tumor
Humans
Hydrogen Peroxide
Hydroxyl Radical
Nanoparticles*
Neoplasms* / drug therapy
Reactive Oxygen Species
Tumor Microenvironment

Substances

Reactive Oxygen Species
Hydroxyl Radical
Hydrogen Peroxide