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

Medulloblastoma is the most common malignant paediatric brain tumour, with ~30% mediated by Sonic hedgehog signalling. Vismodegib-mediated inhibition of the Sonic hedgehog effector Smoothened inhibits tumour growth but causes growth plate fusion at effective doses. Here, we report a nanotherapeutic approach targeting endothelial tumour vasculature to enhance blood-brain barrier crossing. We use fucoidan-based nanocarriers targeting endothelial P-selectin to induce caveolin-1-dependent transcytosis and thus nanocarrier transport into the brain tumour microenvironment in a selective and active manner, the efficiency of which is increased by radiation treatment. In a Sonic hedgehog medulloblastoma animal model,…

• AC
  American Cancer Society

  Award: GC230452
• CF
  Commonwealth Foundation
• HF
  Hartwell Foundation
• MS
  Memorial Sloan-Kettering Cancer Center

  Awards: CA008748, P30-CA008748
• PS
  Pershing Square Sohn Cancer Research Alliance
• CF
  Cycle for Survival

  Award: P30-CA008748
• EC
  Emerson Collective
• WC
  Weill Cornell Medical College
• NC
  National Cancer Institute

  Awards: R01-CA215719, CA008748, CA062948, P30-CA008748
• NI
  National Institute of Neurological Disorders and Stroke

  Award: R01-NS116353