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Nano Research 2023, 16(5): 7280-7292 https://doi.org/10.1007/s12274-023-5377-0
Research Article | Issue | Published: 25 March 2023

Ultrasound cascade regulation of nano-oxygen hybrids triggering ferroptosis augmented sonodynamic anticancer therapy

Show Author's Information Yue Sun1,§,  Yihui Wang1,2,§,  Ruyin Han1,  Ziwei Ren1,  Xin Chen1,  Wenzhuo Dong1,  Stephen Choi3,  Quanhong Liu1,  Xiaobing Wang1( )
Key Laboratory of Medicinal Resources and Natural Pharmaceutical Chemistry, National Engineering Laboratory for Resource Developing of Endangered Chinese Crude Drugs in Northwest China, College of Life Sciences, Shaanxi Normal University, Xi’an 710119, China
Department of Ultrasound Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, China
Kerry Rehabilitation Medicine Research Institute, Shenzhen 518000, China

§ Yue Sun and Yihui Wang contributed equally to this work.

Keywords:
sonodynamic therapy, ferroptosis, nano-oxygen carrier, sono-Fenton, hypoxic tumor environment
Topics:
Nano biology
Cite this article:
Sun Y, Wang Y, Han R, et al. Ultrasound cascade regulation of nano-oxygen hybrids triggering ferroptosis augmented sonodynamic anticancer therapy. Nano Research, 2023, 16(5): 7280-7292. https://doi.org/10.1007/s12274-023-5377-0
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Abstract Full text Electronic supplementary material About this article

Sonodynamic therapy (SDT) has attracted great interest in the field of cancer therapy because of its non-invasiveness, deep penetration, and spatiotemporal controllability. However, the sonodynamic effect is severely hindered by hypoxia and a high glutathione (GSH) level in tumor microenvironment. In this work, a new type of nanohybrid sonosensitizer is designed, which incorporates several prominent advantages of organic, inorganic, and natural sonosensitizers for imaging-guided SDT and ferroptosis induction. As an endogenous transporter, hemoglobin (Hb) has dual functions of oxygen and iron supplement. Apparently, Hb can transport iron to the tumor site for Fe-dependent ferroptosis, yet this oxygen carrier is able to enhance the sensitivity of tumor cells to oxygen-driven SDT. We innovatively hybridized Hb, sinoporphyrin sodium (DVDMS), and titanium dioxide (TiO2) to prepare an integrated nano-oxygen carrier (designated as HDT) for multifarious cancer theranostics, which not only attained satisfactory sonosensitization of DVDMS/TiO2 but also achieved oxygen-boosted SDT and potent ferroptosis via Hb. Under ultrasound irradiation, the oxygenation of HDT markedly amplified the generation of reactive oxygen species (ROS) in hypoxic tumors, promoted the valence transition of Hb to accelerate Fenton reaction, and led to ferroptosis. This strategy virtually eradicated tumors in situ and exhibited immunoregulatory potential for augmenting anti-tumor effects in vivo and in vitro through ROS formation, O2 self-supplement, GSH depletion, and lipid peroxidation. Collectively, HDT demonstrated excellent dual-modal imaging performance, providing a valuable platform for photoacoustic/fluorescence-guided SDT and ferroptosis induction in tumor cells.


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Electronic supplementary material
About this article

Ultrasound cascade regulation of nano-oxygen hybrids triggering ferroptosis augmented sonodynamic anticancer therapy

Show Author's information Yue Sun1,§, Yihui Wang1,2,§, Ruyin Han1, Ziwei Ren1, Xin Chen1, Wenzhuo Dong1, Stephen Choi3, Quanhong Liu1, Xiaobing Wang1( )
Key Laboratory of Medicinal Resources and Natural Pharmaceutical Chemistry, National Engineering Laboratory for Resource Developing of Endangered Chinese Crude Drugs in Northwest China, College of Life Sciences, Shaanxi Normal University, Xi’an 710119, China
Department of Ultrasound Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, China
Kerry Rehabilitation Medicine Research Institute, Shenzhen 518000, China

§ Yue Sun and Yihui Wang contributed equally to this work.

Abstract

Sonodynamic therapy (SDT) has attracted great interest in the field of cancer therapy because of its non-invasiveness, deep penetration, and spatiotemporal controllability. However, the sonodynamic effect is severely hindered by hypoxia and a high glutathione (GSH) level in tumor microenvironment. In this work, a new type of nanohybrid sonosensitizer is designed, which incorporates several prominent advantages of organic, inorganic, and natural sonosensitizers for imaging-guided SDT and ferroptosis induction. As an endogenous transporter, hemoglobin (Hb) has dual functions of oxygen and iron supplement. Apparently, Hb can transport iron to the tumor site for Fe-dependent ferroptosis, yet this oxygen carrier is able to enhance the sensitivity of tumor cells to oxygen-driven SDT. We innovatively hybridized Hb, sinoporphyrin sodium (DVDMS), and titanium dioxide (TiO2) to prepare an integrated nano-oxygen carrier (designated as HDT) for multifarious cancer theranostics, which not only attained satisfactory sonosensitization of DVDMS/TiO2 but also achieved oxygen-boosted SDT and potent ferroptosis via Hb. Under ultrasound irradiation, the oxygenation of HDT markedly amplified the generation of reactive oxygen species (ROS) in hypoxic tumors, promoted the valence transition of Hb to accelerate Fenton reaction, and led to ferroptosis. This strategy virtually eradicated tumors in situ and exhibited immunoregulatory potential for augmenting anti-tumor effects in vivo and in vitro through ROS formation, O2 self-supplement, GSH depletion, and lipid peroxidation. Collectively, HDT demonstrated excellent dual-modal imaging performance, providing a valuable platform for photoacoustic/fluorescence-guided SDT and ferroptosis induction in tumor cells.

Keywords: sonodynamic therapy, ferroptosis, nano-oxygen carrier, sono-Fenton, hypoxic tumor environment

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Publication history
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Acknowledgements

Publication history

Received: 25 August 2022
Revised: 29 November 2022
Accepted: 03 December 2022
Published: 25 March 2023
Issue date: May 2023

Copyright

© Tsinghua University Press 2023

Acknowledgements

Acknowledgements

This work was supported by the Fundamental Research Funds for the Central Universities (No. GK202105004).

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