Multi-functional nanosonosensitizer-engineered bacteria to overcome tumor hypoxia for enhanced sonodynamic therapy.

Autor: Wang T; Key Laboratory of Medical Imaging Precision Theranostics and Radiation Protection, College of Hunan Province, Hengyang Medical School, University of South China, Changsha, PR China; Institute of Medical Imaging, Hengyang Medical School, University of South China, Hengyang, PR China., Du M; Key Laboratory of Medical Imaging Precision Theranostics and Radiation Protection, College of Hunan Province, Hengyang Medical School, University of South China, Changsha, PR China; Institute of Medical Imaging, Hengyang Medical School, University of South China, Hengyang, PR China., Yuan Z; Faculty of Health Sciences, University of Macau, Taipa, Macau SAR, PR China; Centre for Cognitive and Brain Sciences, University of Macau, Taipa, Macau SAR, PR China., Guo J; Faculty of Health Sciences, University of Macau, Taipa, Macau SAR, PR China; Centre for Cognitive and Brain Sciences, University of Macau, Taipa, Macau SAR, PR China., Chen Z; Key Laboratory of Medical Imaging Precision Theranostics and Radiation Protection, College of Hunan Province, Hengyang Medical School, University of South China, Changsha, PR China; Institute of Medical Imaging, Hengyang Medical School, University of South China, Hengyang, PR China; Department of Medical Imaging, The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, Changsha, PR China. Electronic address: zhiyi_chen@usc.edu.cn.
Jazyk: angličtina
Zdroj: Acta biomaterialia [Acta Biomater] 2024 Nov; Vol. 189, pp. 519-531. Date of Electronic Publication: 2024 Oct 10.
DOI: 10.1016/j.actbio.2024.10.013
Abstrakt: Background: Ultrasound-triggered sonodynamic therapy (SDT), with high safety and acceptance, has become a promising tumor treatment. However, the dense stroma, hypoxic microenvironment of tumor, and the unpredictable treatment timing limit the effectiveness of sonosensitizers and the antitumor therapeutic effect. Thus, it is crucial to develop an imaging-guided sensitization strategy for hypoxic tumor sonosensitization to improve the efficacy of SDT.
Methods: In this study, we developed a biohybrid system CB@HPP, which genetically engineered bacteria to express catalase (CB) and modified nanosonosensitizers (HPP) to the surface of these bacteria. Tumor hypoxia relief, tumor targeting, biocompatibility, and antitumor efficacy were evaluated through in vitro and in vivo experiments. In addition, the photoacoustic (PA), ultrasound (US), and fluorescence (FL) imaging effects of CB@HPP were evaluated in vivo and in vitro.
Results: After intravenous injection, CB@HPP was able to target tumor tissue. CB@HPP possessed efficient catalase activity and successfully degraded hydrogen peroxide to produce oxygen. Increased oxygen levels relief intratumoral hypoxia, thereby enhancing CB@HPP-mediated. In addition, CB@HPP showed FL/PA/US multimodal imaging capabilities, which reflects the aggregation effect of CB@HPP in the tumor and suggest the timing of treatment.
Conclusion: The biohybrid system CB@HPP significantly alleviates tumor hypoxia, and multimodal imaging-mediated oxygen-producing SDT effectively suppresses tumors. This integrated imaging and therapeutic biohybrid system provides a more efficient and attractive cancer treatment strategy for SDT.
Statement of Significance: This study developed a sensitizing SDT strategy for imaging-guided drug-targeted delivery and in situ oxygen production. We designed a biohybrid system CB@HPP, which was hybridized by the engineered bacteria with catalytic oxygen production and nanosonosensitizer with multimodal imaging capability. CB@HPP significantly alleviates tumor hypoxia, and multimodal imaging-mediated oxygen-producing SDT effectively suppresses tumors. This integrated imaging and therapeutic biohybrid system provides a more efficient and attractive cancer treatment strategy for SDT.
Competing Interests: Declaration of interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024. Published by Elsevier Ltd.)
Databáze: MEDLINE
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