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

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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 .

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 organization: CAN-PRO - Translational Cancer Medicine Program
Research Programs Unit
Laboratory Animal Centre
Pirjo Maarit Laakkonen / Principal Investigator
Helsinki Institute of Life Science HiLIFE
Date: 2019-04-16
Language: eng
Number of pages: 12
Belongs to series: Journal of Visualized Experiments
ISSN: 1940-087X
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.
Blood-brain tumor-barrier
Cancer Research
CooP peptide
Issue 146
endothelial cell differentiation
endothelial permeability
in vivo imaging
intercellular transport
tumor targeting
3111 Biomedicine
Peer reviewed: Yes
Rights: cc_by_nc_nd
Usage restriction: openAccess
Self-archived version: publishedVersion

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