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  • Perspective
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Engineering nanomaterials for glioblastoma nanovaccination

Abstract

Glioblastoma is a lethal brain cancer with treatment resistance stemming from its interactions with the surrounding microenvironment and obstacles such as the blood–brain barrier. Conventional therapies such as surgery and chemotherapy have shown limited efficacy, whereas immunotherapies, effective in other solid cancers, face obstacles in glioblastoma owing to its unique immunological dysfunction. Despite the development of peptide, neoantigen, cell-based and mRNA-based vaccines, progress to advanced clinical trials has been sluggish. Factors contributing to this slow progress include the immunosuppressive microenvironment of the tumour, the presence of the blood–brain barrier and the inherent instability of glioblastoma vaccines, collectively hindering treatment efficacy. In this context, nanomaterials have emerged as promising owing to their capacity to cross the blood–brain barrier, shield therapeutics from degradation and efficiently target the brain. In this Perspective, we highlight the development of glioblastoma nanovaccination, discussing strategies for nanoparticle engineering to breach the blood–brain barrier and target both immune and glioblastoma cells, paving the way for potential breakthroughs in glioblastoma treatment.

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Fig. 1: Overview of glioblastoma treatment and current clinical trials of glioblastoma vaccines.
Fig. 2: Current and future therapeutic approaches for glioblastoma.
Fig. 3: Strategies to engineer nanoparticles for targeted brain drug delivery using intravenous, intranasal and intracranial routes.
Fig. 4: Mechanism of action of STING nanovaccines, neoantigen nanovaccines and mRNA nanovaccines into the glioblastoma tumour site.

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Acknowledgements

F.S. acknowledges the support from the National Center of Competence in Research (NCCR) Bioinspired Materials through the Swiss National Science Foundation and the Adolphe Merkle Foundation. J. Conde acknowledges the support of the European Research Council (ERC) under the European Union’s Horizon 2020 Research and Innovation Programme (ERC-StG-2019-848325). A.S. acknowledges the support of the European Union under the ERC CoG ‘Smart Nanoparticles’ - 101089009.

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All authors researched data for the article and wrote the article. J. Conde and F.S. contributed substantially to discussion of the content. J. Conde and F.S. reviewed and edited the manuscript before submission.

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Correspondence to João Conde or Flávia Sousa.

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J. Conde is a co-founder and shareholder of TargTex S.A. Targeted Therapeutics for Glioblastoma Multiforme and is a member of the Global Burden Disease (GBD) consortium from Institute for Health Metrics and Evaluation (IHME), University of Washington (USA).

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Hameedat, F., Mendes, B.B., Conniot, J. et al. Engineering nanomaterials for glioblastoma nanovaccination. Nat Rev Mater (2024). https://doi.org/10.1038/s41578-024-00684-z

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