Predicting In Vivo Payloads Delivery using a Blood-brain Tumor-barrier in a Dish

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http://hdl.handle.net/10138/303885

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Le Joncour , V , Karaman , S & Laakkonen , P M 2019 , ' Predicting In Vivo Payloads Delivery using a Blood-brain Tumor-barrier in a Dish ' , Journal of Visualized Experiments , no. 146 , 59384 . https://doi.org/10.3791/59384

Title: Predicting In Vivo Payloads Delivery using a Blood-brain Tumor-barrier in a Dish
Author: Le Joncour, Vadim; Karaman, Sinem; Laakkonen, Pirjo Maarit
Contributor: University of Helsinki, CAN-PRO - Translational Cancer Medicine Program
University of Helsinki, CAN-PRO - Translational Cancer Medicine Program
University of Helsinki, Laboratory Animal Centre
Date: 2019-04-16
Language: eng
Number of pages: 12
Belongs to series: Journal of Visualized Experiments
ISSN: 1940-087X
URI: http://hdl.handle.net/10138/303885
Abstract: Highly selective by nature, the blood-brain barrier (BBB) is essential for the brain homeostasis in physiological conditions. However, in the context of brain tumors, the molecular selectivity of BBB also shields the neoplastic cells by blocking the delivery of peripherally administered chemotherapies. The development of novel drugs (including nanoparticles) targeting malignant brain tumors ideally requires the use of preclinical animal models to study the drug’s transcytosis and antitumor efficacy. In order to comply with the 3R principle (refine, reduce, and replace) to reduce the number of laboratory animals in experimental setup and perform the high-throughput screening of a large library of antitumor agents, we developed a reproducible in vitro human and murine mimic of the blood-brain tumor-barrier (BBTB) using three-layered cultures of endothelial cells, astrocytes, and patient-derived glioblastoma spheres. For higher scalability and reproducibility, commercial cell lines or immortalized cells have been used in tailored conditions to allow the formation of a barrier resembling the actual BBB. Here we describe a protocol to obtain a BBTB mimic by culturing endothelial cells in contact with astrocytes at specific cell densities on inserts. This BBTB mimic can be used, for instance, for the quantification and confocal imaging of the nanoparticle passage through the endothelial and astrocytic barriers, in addition to the evaluation of the tumor cell targeting within the same assay. Moreover, we show that the obtained data can be used to predict the behavior of nanoparticles in preclinical animal models. In a broader perspective, this in vitro model could be adapted to other neurodegenerative diseases for the determination of the passage of new therapeutic molecules through the BBB and/or be supplemented with brain organoids to directly evaluate the efficacy of drugs.
Subject: ASTROCYTES
Blood-brain tumor-barrier
CAPTURE
Cancer Research
CooP peptide
DISRUPTION
DRUG-DELIVERY
ENDOTHELIAL-CELLS
Issue 146
NANOPARTICLES
PERICYTES
VASCULAR-PERMEABILITY
VITRO MODELS
astrocytes
co-cultures
endothelial cell differentiation
endothelial permeability
glioblastoma
in vivo imaging
intercellular transport
nanoparticles
tumor targeting
3111 Biomedicine
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