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Multi-antitumor therapy and synchronous imaging monitoring based on exosome

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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Background

Tumor-derived exosomes (TEX) have shown great potential for drug delivery and tumor targeting. Here, we developed a novel multi-drug loaded exosomes nanoprobe for combined antitumor chemotherapy and photodynamic therapy, and monitoring the drug delivery capabilities with pre-targeting technique.

Methods

TEX of human colorectal cancer HCT116 was prepared, and Doxorubicin and the photodynamic therapy agent 5-aminolevulinic acid (ALA) were loaded and named as TEX@DOX@ALA. Tumor uptake was first examined using fluorescence imaging of the fluorescent dye Cy5 (TEX@DOX@ALA@Cy5). Visualization of exosome aggregation in tumor were realized by positron-emission tomography/computed tomography (PET/CT) with pre-targeting technique. Tumor-bearing mice were first injected with TEX@DOX@ALA labeled with azide (N3) (TEX@DOX@ALA@N3), and then 68Ga-(2,2′-((6-amino-1-(4,7-bis (carboxymethyl)-1,4,7-triazonan-1-yl) hexan-2-yl) azanediyl) diacetic acid-dibenzocyclooctyne (68Ga-L-NETA-DBCO) was injected after 24 h for PET/CT imaging via in vivo click chemistry. For the antitumor therapy with photodynamic and/or chemotherapy, seven groups of tumor-bearing mice with different therapy were monitored, and the tumor size, animal weight and the survival time were recorded. Furthermore, the samples of blood and interested tissues (heart, lung, liver, kidney, and spleen) were harvested for hematological analysis and H&E staining.

Results

The drug loading process did not influence the structure or the function of the HCT116 TEX membranes. In a fluorescence imaging experiment, higher fluorescence could be seen in tumor after TEX@DOX@ALA@Cy5 injected, and reached the highest signal at 24 h. From PET/CT images with subcutaneous and orthotopic colon tumor-bearing mice, clear radioactivity could be seen in tumors, which suggested the successes of TEX accumulation in tumors. TEX@DOX@ALA group with photodynamic therapy and chemotherapy had the best tumor inhibition effect compared with the other groups, with the longest survival time (36 days, 37.5%). No significant damage was found on histological observation and the blood biochemical analysis, which suggested the safety of the multi-drug loaded exosomes.

Conclusions

We successfully engineered an exosome-based nanoprobe integrating PET imaging components and therapeutic drugs. This drug-loaded exosome system may effectively target tumors and enable synergistic chemotherapeutic and photodynamic antitumor effects.

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Acknowledgements

We would like to thank Ms. Guang-Xin Wang and Ms. Yan Wang at The Analysis and Testing Center of Institute of Hydrobiology, Chinese Academy of Sciences for discussion and comments on the manuscript. We would also like to acknowledge the service provided by Beijing novel medical equipment Ltd. for image acquisition.

Funding

This work was supported by the National Natural Science Foundation of China (No. 81873904 and 82071966).

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Author notes

  1. Ruijie Qian aand Boping Jing contributed equally to this work.

Authors and Affiliations

  1. Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Jiefang Ave, Wuhan, 430022, China

    Ruijie Qian, Boping Jing, Dawei Jiang, Yongkang Gai, Ziyang Zhu, Xiaojuan Huang, Yu Gao, Xiaoli Lan & Rui An

  2. Hubei Key Laboratory of Molecular Imaging, Wuhan, 430022, China

    Ruijie Qian, Boping Jing, Dawei Jiang, Yongkang Gai, Ziyang Zhu, Yu Gao, Xiaoli Lan & Rui An

  3. Department of Ultrasound, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China

    Boping Jing

  4. Department of Nuclear Medicine, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China

    Xiaojuan Huang

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  1. Ruijie Qian
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Correspondence to Xiaoli Lan or Rui An.

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Ethics approval and consent to participate

All experimental schemes were performed under the guidance and approved by the Institutional Animal Care and Use Committee of Tongji Medical College of Huazhong University of Science and Technology. BALB/c nude mice (female, 5-6 weeks old) purchased from Weitong Lihua Laboratory Animal Center (Beijing, China), and maintained in a pathogen-free environment. Extensive efforts were made to ensure minimal suffering of the animals used during the study.

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The authors have declared that no competing interest exists.

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Qian, R., Jing, B., Jiang, D. et al. Multi-antitumor therapy and synchronous imaging monitoring based on exosome. Eur J Nucl Med Mol Imaging 49, 2668–2681 (2022). https://doi.org/10.1007/s00259-022-05696-x

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