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Aptamer-functionalized nanoplatforms overcoming temozolomide resistance in synergistic chemo/photothermal therapy through alleviating tumor hypoxia

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Abstract

Tumor hypoxia is intimately associated with gliomas, which represents a significant threat to human health and are resistant to the first-line chemotherapeutic drug temozolomide (TMZ) due to hypoxia. In this work, to overcome TMZ resistance in orthotopic gliomas, aptamer-functionalized liposomes are manufactured to encapsulate TMZ and photothermal agent IR780, and can cross the blood-brain barrier and actively target gliomas. It is possible to employ liposomes for both fluorescence and photoacoustic imaging simultaneously due to their stability and excellent photothermal conversion capabilities. This chemo/photothermal synergistic therapeutic effect of liposomes on gliomas is demonstrated by their abilities to target orthotopic gliomas, alleviate tumor hypoxia and consequently reverse resistance of glioma cells to TMZ, thereby extending the survival time of tumor-bearing mice, making the nanoplatforms and their synergistic chemo/photothermal therapy as a potential clinical treatment for gliomas.

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Acknowledgements

This work was supported, in part, by the National Natural Science Foundation of China (Nos. 32171173, 32001074, and 82260473), the Key Research and Development Program in Ningxia Province of China (No. 2022BEG03080), the Natural Science Basic Research Plan in Ningxia Province of China (No. 2022AAC03522), the Health Commission of Ningxia Hui Autonomous Region Science and Technology Support Project for Quality Development of Medical Institutions (No. 2023-NWKYT-019), the State Key Laboratory Grant of Space Medicine Fundamentals and Application (No. SMFA20A02), the Natural Science Basic Research Key Program of Shaanxi Province (No. 2023-JC-ZD-53), the Natural Science Basic Research Plan in Shaanxi Province of China (No. 2022JQ-201), the Fundamental Research Funds for the Central Universities (Nos. ZYTS23190 and xzy012022134), and the Beijing Xisike Clinical Oncology Research Foundation.

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Authors and Affiliations

  1. School of Life Science and Technology, Xidian University and Engineering Research Center of Molecular and Neuro Imaging, Ministry of Education, Xi’an, 710126, China

    Yun Zeng, Linfei Zhao, Dan Chen & Yonghua Zhan

  2. Department of Radiation Oncology, General Hospital of Ningxia Medical University, Yinchuan, 750004, China

    Changhu Liu & Wenhua Zhan

  3. International Joint Research Center for Advanced Medical Imaging and Intelligent Diagnosis and Treatment and Xi’an Key Laboratory of Intelligent Sensing and Regulation of trans-Scale Life Information, School of Life Science and Technology, Xidian University, Xi’an, 710126, China

    Yun Zeng, Linfei Zhao, Dan Chen & Yonghua Zhan

  4. Xi’an Key Laboratory for Prevention and Treatment of Common Aging Diseases, Translational and Research Centre for Prevention and Therapy of Chronic Disease, Institute of Basic and Translational Medicine, Xi’an Medical University, Xi’an, 710021, China

    Ke Li

  5. Radiology Department, CT and MRI Room, Ninth Hospital of Xi’an, Xi’an, 710054, China

    Jingwen Ma

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  1. Yun Zeng
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  2. Linfei Zhao
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  5. Dan Chen
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  6. Changhu Liu
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  7. Wenhua Zhan
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Correspondence to Wenhua Zhan or Yonghua Zhan.

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Aptamer-functionalized nanoplatforms overcoming temozolomide resistance in synergistic chemo/photothermal therapy through alleviating tumor hypoxia

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Zeng, Y., Zhao, L., Li, K. et al. Aptamer-functionalized nanoplatforms overcoming temozolomide resistance in synergistic chemo/photothermal therapy through alleviating tumor hypoxia. Nano Res. 16, 9859–9872 (2023). https://doi.org/10.1007/s12274-023-5742-7

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