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Glioma cell membrane camouflaged cinobufotalin delivery system for combinatorial orthotopic glioblastoma therapy

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Abstract

Glioblastoma (GBM) belongs to the deadliest primary malignancies with high mortality rate and poor prognosis. Over the past decades, less progress has been made to treat GBM, owing largely to the lack of effective chemotherapeutics and poor drug accumulation in the glioma tissue. In order to address this issue, we present an efficient biomimetic nanocomposite (Cu2−xSe-CB@MEM, CCM), consisting of Cu2−xSe nanoparticle core modified by cinobufotalin (CB), a toad venom extract, which is camouflaged with glioma cell Ln229 membrane. It is demonstrated that CB can decrease the protein activity of inosine monophosphate dehydrogenase 1 (IMPDH1), a key target correlated with prognosis, through intermolecular hydrogen bonding with amino acid residues ARG-105 and ASP-77. The glioma cell membrane-camouflage endows the CCM with blood-brain barrier penetration and homology tumor-targeted ability. The optimized cinobufotalin based chemotherapy combining with the near-infrared-II (NIR-II) irradiation shows outstanding inhibition effect to glioma cells, by blocking cell cycle and inducing apoptosis. In vivo mice bearing orthotopic Ln229 GBM treated with CCM+NIR-II (CCM+L) have significantly suppressed tumor growth and extended survival, without side effect. The glioma cell membrane camouflaged nanocomposite of Cu2−xSe and cinobufotalin with its significant anti-glioma property and well biosafety will provide novel alternatives for clinical treatment of GBM.

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Acknowledgements

This work was supported by the National Nature Science Fund of China (Nos. 81872064 and 82272879), the Natural Science Fund of Guangdong Province, China (No. 2021A1515012465), Technology Program of Guangzhou (No. 202206010068) and Major Discipline and Academic Leader Training Program of Jiangxi Province (No. 20225BCJ23001). The authors thank Peng Zhao and Ye Song for their technical assistance.

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  1. Zibin Song, Liqian Zhao, and Weiyi Fang contributed equally to this work.

Authors and Affiliations

  1. Department of Neurosurgery, Southern Medical University Nanfang Hospital, Guangzhou, 510515, China

    Zibin Song, Liqian Zhao, Zhengming Zhan, Yonghua Cai, ShuaiShuai Xue, Peng Chai & Ye Song

  2. Institute of Brain Diseases, Nanfang Hospital of Southern Medical University, Guangzhou, 510515, China

    Zibin Song, Liqian Zhao, Zhengming Zhan, Yonghua Cai, ShuaiShuai Xue, Peng Chai & Ye Song

  3. Cancer Center, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou, 510515, China

    Weiyi Fang

  4. NMPA Key Laboratory for Research and Evaluation of Drug Metabolism Guangdong, Provincial Key Laboratory of Cardiac Function and Microcirculation Guangdong, Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, China

    Siyun Guo, Anqi Xu & Peng Zhao

  5. Department of Neurosurgery, Ganzhou People’s Hospital, Ganzhou, 341000, China

    Qiuhua Jiang & Ye Song

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  1. Zibin Song
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  11. Peng Zhao
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Correspondence to Qiuhua Jiang, Peng Zhao or Ye Song.

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Song, Z., Zhao, L., Fang, W. et al. Glioma cell membrane camouflaged cinobufotalin delivery system for combinatorial orthotopic glioblastoma therapy. Nano Res. 16, 11164–11175 (2023). https://doi.org/10.1007/s12274-023-5807-7

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