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Nano Research 2023, 16(1): 782-791 https://doi.org/10.1007/s12274-022-4646-2
Research Article | Issue | Published: 28 July 2022

Platelet membrane-coated C-TiO2 hollow nanospheres for combined sonodynamic and alkyl-radical cancer therapy

Show Author's Information Weihong Guo4,§,  Tao Wang2,§,  Chunyu Huang1,5,§,  Shipeng Ning6,§,  Qinglong Guo2,  Wei Zhang3,  Huawei Yang6,  Daoming Zhu4,  Qinqin Huang1( ),  Haisheng Qian3,  Xianwen Wang3( )
Department of Molecular Pathology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou 450014, China
Department of Orthopaedics, The Second Hospital of Anhui Medical University, Hefei 230601, China
School of Biomedical Engineering, Research and Engineering Center of Biomedical Materials, Anhui Medical University, Hefei 230032, China
Department of General Surgery & Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, The First School of Clinical Medicine, Southern Medical University, Guangzhou 510515, China
Department of Radiation and Medical Oncology, Hubei Key Laboratory of Tumor Biological Behaviors, Hubei Cancer Clinical Study Center, Zhongnan Hospital of Wuhan University, Wuhan 430071, China
Department of Breast Surgery, Guangxi Medical University Cancer Hospital, Nanning 530000, China

§ Weihong Guo, Tao Wang, Chunyu Huang, and Shipeng Ning contributed equally to this work.

Keywords:
combination therapy, sonodynamic therapy, C-TiO2, alkyl-radical therapy, biomimetic nanomaterials
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Guo W, Wang T, Huang C, et al. Platelet membrane-coated C-TiO2 hollow nanospheres for combined sonodynamic and alkyl-radical cancer therapy. Nano Research, 2023, 16(1): 782-791. https://doi.org/10.1007/s12274-022-4646-2
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Abstract Full text Electronic supplementary material About this article

The therapeutic efficiency of sonodynamic therapy (SDT) mainly depends on the presence of oxygen (O2) to generate harmful reactive oxygen species (ROS); thus, the hypoxic tumor microenvironment significantly limits the efficacy of SDT. Therefore, the development of oxygen-independent free radical generators and associated combination therapy tactics can be a promising field to facilitate the anticancer capability of SDT. In this study, a biomimetic drug delivery system (C-TiO2/AIPH@PM) composed of an alkyl-radical generator (2,2′-azobis[2-(2-imidazolin-2-yl)propane] dihydrochloride, AIPH)-loaded C-TiO2 hollow nanoshells (HNSs) as the inner cores, and a platelet membrane (PM) as the outer shells is successfully prepared for synergistic SDT and oxygen-independent alkyl-radical therapy. The PM encapsulation can significantly prolong the blood circulation time of C-TiO2/AIPH@PM compared with C-TiO2/AIPH while enabling C-TiO2/AIPH@PM to achieve tumor targeting. C-TiO2/AIPH@PM can efficiently produce ROS and alkyl radicals, which can achieve a more thorough tumor eradication regardless of the normoxic or hypoxic conditions. Furthermore, the generation of these radicals improves the efficiency of SDT. In addition, nitrogen (N2) produced due to the decomposition of AIPH enhances the acoustic cavitation effect and lowers the cavitation threshold, thereby enhancing the penetration of C-TiO2/AIPH@PM at the tumor sites. Both in vitro and in vivo experiments demonstrate that C-TiO2/AIPH@PM possesses good biosafety, ultrasound imaging performance, and excellent anticancer efficacy. This study provides a new strategy to achieve oxygen-independent free radical production and enhance therapeutic efficacy by combining SDT and free radical therapy.


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Electronic supplementary material
About this article

Platelet membrane-coated C-TiO2 hollow nanospheres for combined sonodynamic and alkyl-radical cancer therapy

Show Author's information Weihong Guo4,§, Tao Wang2,§, Chunyu Huang1,5,§, Shipeng Ning6,§, Qinglong Guo2, Wei Zhang3, Huawei Yang6, Daoming Zhu4, Qinqin Huang1( ), Haisheng Qian3, Xianwen Wang3( )
Department of Molecular Pathology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou 450014, China
Department of Orthopaedics, The Second Hospital of Anhui Medical University, Hefei 230601, China
School of Biomedical Engineering, Research and Engineering Center of Biomedical Materials, Anhui Medical University, Hefei 230032, China
Department of General Surgery & Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, The First School of Clinical Medicine, Southern Medical University, Guangzhou 510515, China
Department of Radiation and Medical Oncology, Hubei Key Laboratory of Tumor Biological Behaviors, Hubei Cancer Clinical Study Center, Zhongnan Hospital of Wuhan University, Wuhan 430071, China
Department of Breast Surgery, Guangxi Medical University Cancer Hospital, Nanning 530000, China

§ Weihong Guo, Tao Wang, Chunyu Huang, and Shipeng Ning contributed equally to this work.

Abstract

The therapeutic efficiency of sonodynamic therapy (SDT) mainly depends on the presence of oxygen (O2) to generate harmful reactive oxygen species (ROS); thus, the hypoxic tumor microenvironment significantly limits the efficacy of SDT. Therefore, the development of oxygen-independent free radical generators and associated combination therapy tactics can be a promising field to facilitate the anticancer capability of SDT. In this study, a biomimetic drug delivery system (C-TiO2/AIPH@PM) composed of an alkyl-radical generator (2,2′-azobis[2-(2-imidazolin-2-yl)propane] dihydrochloride, AIPH)-loaded C-TiO2 hollow nanoshells (HNSs) as the inner cores, and a platelet membrane (PM) as the outer shells is successfully prepared for synergistic SDT and oxygen-independent alkyl-radical therapy. The PM encapsulation can significantly prolong the blood circulation time of C-TiO2/AIPH@PM compared with C-TiO2/AIPH while enabling C-TiO2/AIPH@PM to achieve tumor targeting. C-TiO2/AIPH@PM can efficiently produce ROS and alkyl radicals, which can achieve a more thorough tumor eradication regardless of the normoxic or hypoxic conditions. Furthermore, the generation of these radicals improves the efficiency of SDT. In addition, nitrogen (N2) produced due to the decomposition of AIPH enhances the acoustic cavitation effect and lowers the cavitation threshold, thereby enhancing the penetration of C-TiO2/AIPH@PM at the tumor sites. Both in vitro and in vivo experiments demonstrate that C-TiO2/AIPH@PM possesses good biosafety, ultrasound imaging performance, and excellent anticancer efficacy. This study provides a new strategy to achieve oxygen-independent free radical production and enhance therapeutic efficacy by combining SDT and free radical therapy.

Keywords: combination therapy, sonodynamic therapy, C-TiO2, alkyl-radical therapy, biomimetic nanomaterials

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Publication history
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Acknowledgements

Publication history

Received: 11 May 2022
Revised: 09 June 2022
Accepted: 09 June 2022
Published: 28 July 2022
Issue date: January 2023

Copyright

© Tsinghua University Press 2022

Acknowledgements

This work was supported by the Research fund of Anhui Institute of Translation Medicine (No. 2021zhyx-C49), the Foundation of Anhui Medical University (No. 2021xkj030), the Anhui Provincial Natural Science Foundation (No. 2208085QC81), the Basic and Clinical Cooperative Research and Promotion Program of Anhui Medical University (No. 2021xkjT028), and Grants for Scientific Research of BSKY from Anhui Medical University (No. 1406012201). The authors would like to thank the shiyanjia lab (www. shiyanjia.com) for the XPS test.

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