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Research Article

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

Zibin Song1,2,§, Liqian Zhao1,2,§, Weiyi Fang3,§, Siyun Guo4, Anqi Xu4, Zhengming Zhan1,2, Yonghua Cai1,2, ShuaiShuai Xue1,2, Peng Chai1,2, Qiuhua Jiang5( ), Peng Zhao4( ), Ye Song1,2,5( )
Department of Neurosurgery, Southern Medical University Nanfang Hospital, Guangzhou 510515, China
Institute of Brain Diseases, Nanfang Hospital of Southern Medical University, Guangzhou 510515, China
Cancer Center, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China
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
Department of Neurosurgery, Ganzhou People's Hospital, Ganzhou 341000, China

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

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Graphical Abstract

We construct a biomimetic nanocarrier (Cu2−xSe-CB@MEM, CCM), consisting of Cu2−xSe nanoparticle modified by cinobufotalin (CB), camouflaged with Ln229 membrane. The optimized cinobufotalin based chemotherapy combining with the near-infrared-II (NIR-II) irradiation induces glioblastoma cell cycle arrest and promotes apoptosis.

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.

Keywords

glioblastomacinobufotalinbiomimeticsphotothermal therapyblood-brain barrier

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Nano Research
Volume 16 Issue 8,
August 2023
Pages 11164-11175
DOI: 10.1007/s12274-023-5807-7
Cite this article:
Song Z, Zhao L, Fang W, et al. Glioma cell membrane camouflaged cinobufotalin delivery system for combinatorial orthotopic glioblastoma therapy. Nano Research, 2023, 16(8): 11164-11175. https://doi.org/10.1007/s12274-023-5807-7
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Received: 02 February 2023
Revised: 29 April 2023
Accepted: 05 May 2023
Published: 09 June 2023
© Tsinghua University Press 2023
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