Transient and Efficient Vascular Permeability Window for Adjuvant Drug Delivery Triggered by Microbeam Radiation.

Détails

ID Serval
serval:BIB_61E642774FA0
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Transient and Efficient Vascular Permeability Window for Adjuvant Drug Delivery Triggered by Microbeam Radiation.
Périodique
Cancers
Auteur⸱e⸱s
Sabatasso S., Fernandez-Palomo C., Hlushchuk R., Fazzari J., Tschanz S., Pellicioli P., Krisch M., Laissue J.A., Djonov V.
ISSN
2072-6694 (Print)
ISSN-L
2072-6694
Statut éditorial
Publié
Date de publication
27/04/2021
Peer-reviewed
Oui
Volume
13
Numéro
9
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: epublish
Résumé
Microbeam Radiation Therapy (MRT) induces a transient vascular permeability window, which offers a novel drug-delivery system for the preferential accumulation of therapeutic compounds in tumors. MRT is a preclinical cancer treatment modality that spatially fractionates synchrotron X-rays into micrometer-wide planar microbeams which can induce transient vascular permeability, especially in the immature tumor vessels, without compromising vascular perfusion. Here, we characterized this phenomenon using Chicken Chorioallantoic Membrane (CAM) and demonstrated its therapeutic potential in human glioblastoma xenografts in mice.
the developing CAM was exposed to planar-microbeams of 75 Gy peak dose with Synchrotron X-rays. Similarly, mice harboring human glioblastoma xenografts were exposed to peak microbeam doses of 150 Gy, followed by treatment with Cisplatin. Tumor progression was documented by Magnetic Resonance Imaging (MRI) and caliper measurements.
CAM exposed to MRT exhibited vascular permeability, beginning 15 min post-irradiation, reaching its peak from 45 min to 2 h, and ending by 4 h. We have deemed this period the "permeability window". Morphological analysis showed partially fragmented endothelial walls as the cause of the increased transport of FITC-Dextran into the surrounding tissue and the extravasation of 100 nm microspheres (representing the upper range of nanoparticles). In the human glioblastoma xenografts, MRI measurements showed that the combined treatment dramatically reduced the tumor size by 2.75-fold and 5.25-fold, respectively, compared to MRT or Cisplatin alone.
MRT provides a novel mechanism for drug delivery by increasing vascular transpermeability while preserving vessel integrity. This permeability window increases the therapeutic index of currently available chemotherapeutics and could be combined with other therapeutic agents such as Nanoparticles/Antibodies/etc.
Mots-clé
Chicken Chorioallantoic Membrane (CAM), U-87 Glioblastoma, drug delivery system, microbeam radiation therapy (MRT), vascular permeability
Pubmed
Web of science
Open Access
Oui
Création de la notice
12/04/2022 15:01
Dernière modification de la notice
13/04/2022 5:36
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