From cells to organoids: The evolution of blood-brain barrier technology for modelling drug delivery in brain cancer

Estrella Gonzales-Aloy; Aria Ahmed-Cox; Maria Tsoli; David S Ziegler; Maria Kavallaris

doi:10.1016/j.addr.2023.114777

From cells to organoids: The evolution of blood-brain barrier technology for modelling drug delivery in brain cancer

Adv Drug Deliv Rev. 2023 May:196:114777. doi: 10.1016/j.addr.2023.114777. Epub 2023 Mar 16.

Authors

Estrella Gonzales-Aloy¹, Aria Ahmed-Cox², Maria Tsoli³, David S Ziegler⁴, Maria Kavallaris⁵

Affiliations

¹ Children's Cancer Institute, Lowy Cancer Research Center, UNSW Sydney, NSW, Australia; Australian Center for NanoMedicine, UNSW Sydney, NSW, Australia; School of Clinical Medicine, Faculty of Medicine and Health, UNSW Sydney, NSW, Australia.
² Children's Cancer Institute, Lowy Cancer Research Center, UNSW Sydney, NSW, Australia; Australian Center for NanoMedicine, UNSW Sydney, NSW, Australia; School of Clinical Medicine, Faculty of Medicine and Health, UNSW Sydney, NSW, Australia; Katharina Gaus Light Microscopy Facility, Mark Wainright Analytical Center, UNSW Sydney, NSW, Australia.
³ Children's Cancer Institute, Lowy Cancer Research Center, UNSW Sydney, NSW, Australia; School of Clinical Medicine, Faculty of Medicine and Health, UNSW Sydney, NSW, Australia.
⁴ Children's Cancer Institute, Lowy Cancer Research Center, UNSW Sydney, NSW, Australia; School of Clinical Medicine, Faculty of Medicine and Health, UNSW Sydney, NSW, Australia; Kids Cancer Center, Sydney Children's Hospital, Randwick, NSW, Australia.
⁵ Children's Cancer Institute, Lowy Cancer Research Center, UNSW Sydney, NSW, Australia; Australian Center for NanoMedicine, UNSW Sydney, NSW, Australia; School of Clinical Medicine, Faculty of Medicine and Health, UNSW Sydney, NSW, Australia; UNSW RNA Institute, UNSW Sydney, NSW, Australia. Electronic address: m.kavallaris@ccia.unsw.edu.au.

PMID: 36931346
DOI: 10.1016/j.addr.2023.114777

Abstract

Brain cancer remains the deadliest cancer. The blood-brain barrier (BBB) is impenetrable to most drugs and is a complex 3D network of multiple cell types including endothelial cells, astrocytes, and pericytes. In brain cancers, the BBB becomes disrupted during tumor progression and forms the blood-brain tumor barrier (BBTB). To advance therapeutic development, there is a critical need for physiologically relevant BBB in vitro models. 3D cell systems are emerging as valuable preclinical models to accelerate discoveries for diseases. Given the versatility and capability of 3D cell models, their potential for modelling the BBB and BBTB is reviewed. Technological advances of BBB models and challenges of in vitro modelling the BBTB, and application of these models as tools for assessing therapeutics and nano drug delivery, are discussed. Quantitative, in vitro BBB models that are predictive of effective brain cancer therapies will be invaluable for accelerating advancing new treatments to the clinic.

Keywords: Blood–brain tumor barrier; Drug delivery; Drug screening; Glioblastoma; Microfluidics; Nanoparticles; Organoid; Spheroid; Transwell.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Blood-Brain Barrier* / metabolism
Brain / pathology
Brain Neoplasms* / pathology
Endothelial Cells
Humans
Organoids / pathology