What question did this study set out to answer?

To develop a targeted nanotherapeutic delivery platform that crosses the blood–brain barrier to deliver vismodegib selectively into Sonic hedgehog medulloblastoma while avoiding toxic side effects.

March 1, 2023Nature MaterialsOpen Access

P-selectin-targeted nanocarriers induce active crossing of the blood–brain barrier via caveolin-1-dependent transcytosis

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Authors

DTDaniel TylawskyMemorial Sloan Kettering Cancer Center HKHiroto KiguchiMemorial Sloan Kettering Cancer Center JVJake VaynshteynIcahn School of Medicine at Mount Sinai

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Implication

Preclinical study reveals targeted nanoparticle transcytosis delivers vismodegib safely in medulloblastoma models, highlighting a potent central nervous system delivery strategy.

Key Points

To develop a targeted nanotherapeutic delivery platform that crosses the blood–brain barrier to deliver vismodegib selectively into Sonic hedgehog medulloblastoma while avoiding toxic side effects.
Engineered fucoidan-based nanocarriers targeting endothelial P-selectin to trigger caveolin-1-dependent transcytosis across the blood–brain barrier, evaluating transport alone and combined with radiation.
Tested fucoidan nanoparticles encapsulating the Smoothened inhibitor vismodegib in a Sonic hedgehog medulloblastoma animal model to assess therapeutic efficacy, healthy brain drug exposure, and bone toxicity.
Targeting P-selectin stimulated active, selective caveolin-1-dependent transcytosis into the brain tumour microenvironment, with transcytosis efficiency markedly enhanced by radiation therapy.
Vismodegib-loaded fucoidan nanoparticles demonstrated pronounced anti-tumour efficacy in medulloblastoma models while substantially reducing drug exposure in healthy brain tissue and preventing growth plate fusion toxicity.

Cite This Study

Tylawsky et al. (2023) studied this question.

synapsesocial.com/papers/6a7f3441b1a7ff7f700dfde5 https://doi.org/10.1038/s41563-023-01481-9

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Implication

Preclinical study reveals targeted nanoparticle transcytosis delivers vismodegib safely in medulloblastoma models, highlighting a potent central nervous system delivery strategy.

P-selectin-targeted nanocarriers induce active crossing of the blood–brain barrier via caveolin-1-dependent transcytosis

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Implication

Key Points

Cite This Study

P-selectin-targeted nanocarriers induce active crossing of the blood–brain barrier via caveolin-1-dependent transcytosis

Discussion

Member takes

Implication

Key Points

Cite This Study

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