Cancer cell-mitochondria hybrid membrane coated Gboxin loaded nanomedicines for glioblastoma treatment

Yan Zou, Yajing Sun, Yibin Wang, Dongya Zhang, Huiqing Yang, Xin Wang, Meng Zheng and Bingyang Shi ()
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Yan Zou: Henan-Macquarie University Joint Centre for Biomedical Innovation, Henan Key Laboratory of Brain Targeted Bio-nanomedicine, School of Life Sciences, Henan University
Yajing Sun: Henan-Macquarie University Joint Centre for Biomedical Innovation, Henan Key Laboratory of Brain Targeted Bio-nanomedicine, School of Life Sciences, Henan University
Yibin Wang: Henan-Macquarie University Joint Centre for Biomedical Innovation, Henan Key Laboratory of Brain Targeted Bio-nanomedicine, School of Life Sciences, Henan University
Dongya Zhang: Henan-Macquarie University Joint Centre for Biomedical Innovation, Henan Key Laboratory of Brain Targeted Bio-nanomedicine, School of Life Sciences, Henan University
Huiqing Yang: Henan-Macquarie University Joint Centre for Biomedical Innovation, Henan Key Laboratory of Brain Targeted Bio-nanomedicine, School of Life Sciences, Henan University
Xin Wang: Henan-Macquarie University Joint Centre for Biomedical Innovation, Henan Key Laboratory of Brain Targeted Bio-nanomedicine, School of Life Sciences, Henan University
Meng Zheng: Henan-Macquarie University Joint Centre for Biomedical Innovation, Henan Key Laboratory of Brain Targeted Bio-nanomedicine, School of Life Sciences, Henan University
Bingyang Shi: Henan-Macquarie University Joint Centre for Biomedical Innovation, Henan Key Laboratory of Brain Targeted Bio-nanomedicine, School of Life Sciences, Henan University

Nature Communications, 2023, vol. 14, issue 1, 1-19

Abstract: Abstract Glioblastoma (GBM) remains the most lethal malignant tumours. Gboxin, an oxidative phosphorylation inhibitor, specifically restrains GBM growth by inhibiting the activity of F0F1 ATPase complex V. However, its anti-GBM effect is seriously limited by poor blood circulation, the blood brain barrier (BBB) and non-specific GBM tissue/cell uptake, leading to insufficient Gboxin accumulation at GBM sites, which limits its further clinical application. Here we present a biomimetic nanomedicine (HM-NPs@G) by coating cancer cell-mitochondria hybrid membrane (HM) on the surface of Gboxin-loaded nanoparticles. An additional design element uses a reactive oxygen species responsive polymer to facilitate at-site Gboxin release. The HM camouflaging endows HM-NPs@G with unique features including good biocompatibility, improved pharmacokinetic profile, efficient BBB permeability and homotypic dual tumour cell and mitochondria targeting. The results suggest that HM-NPs@G achieve improved blood circulation (4.90 h versus 0.47 h of free Gboxin) and tumour accumulation (7.73% ID/g versus 1.06% ID/g shown by free Gboxin). Effective tumour inhibition in orthotopic U87MG GBM and patient derived X01 GBM stem cell xenografts in female mice with extended survival time and negligible side effects are also noted. We believe that the biomimetic Gboxin nanomedicine represents a promising treatment for brain tumours with clinical potential.

Date: 2023
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DOI: 10.1038/s41467-023-40280-3

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