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Nanomodulators targeting endothelial WNT and pericytes to reversibly open the blood–tumor barrier for boosted brain tumor therapy.
- Source :
-
Journal of Controlled Release . May2024, Vol. 369, p458-474. 17p. - Publication Year :
- 2024
-
Abstract
- The blood–brain barrier (BBB)/blood–tumor barrier (BTB) impedes brain entry of most brain-targeted drugs, whether they are water-soluble or hydrophobic. Endothelial WNT signaling and neoplastic pericytes maintain BTB low permeability by regulating tight junctions. Here, we proposed nitazoxanide (NTZ) and ibrutinib (IBR) co-loaded ICAM-1-targeting nanoparticles (NI@I-NPs) to disrupt the BTB in a time-dependent, reversible, and size-selective manner by targeting specific ICAM-1, inactivating WNT signaling and depleting pericytes in tumor-associated blood vessels in breast cancer brain metastases. At the optimal NTZ/IBR mass ratio (1:2), BTB opening reached the optimum effect at 48–72 h without any sign of intracranial edema and cognitive impairment. The combination of NI@I-NPs and chemotherapeutic drugs (doxorubicin and etoposide) extended the median survival of mice with breast cancer brain metastases. Targeting BTB endothelial WNT signaling and tumor pericytes via NI@I-NPs could open the BTB to improve chemotherapeutic efficiency against brain metastases. [Display omitted] • Endothelial WNT signaling is activated in brain metastases to keep tight junctions. • Pericytes also contribute to low vascular permeability of brain metastases. • ICAM-1 could mediate drug delivery to silence BTB WNT and deplete tumor pericytes. • Nanomodulators could open the BTB for boosted drug delivery and brain tumor therapy. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 01683659
- Volume :
- 369
- Database :
- Academic Search Index
- Journal :
- Journal of Controlled Release
- Publication Type :
- Academic Journal
- Accession number :
- 177353304
- Full Text :
- https://doi.org/10.1016/j.jconrel.2024.03.047