Blood-brain barrier receptors and transporters: an insight on their function and how to exploit them through nanotechnology

ABSTRACT

Introduction: The blood-brain barrier (BBB) is a highly limiting barrier that prevents the brain from contacting with several circulating molecules, including harmful agents. However, certain systemic nutrients and macromolecules are able to cross the BBB and reach the brain parenchyma, involving the interaction with multiple receptors and/or transporters at the BBB surface. Nanotechnology allows the creation of drug vehicles, functionalized with targeting ligands for binding specific BBB receptors and/or transporters, hence triggering the transport through this biobarrier.

Areas covered: This review focuses the BBB receptors/transporters to be exploited in regard to their overall structure and biologic function, as well as their role in the development of strategies envisaging drug delivery to the brain. Then, the interplay between the targeting of these BBB receptors/transporters and nanotechnology is explored, as they can increase by several-fold the effectiveness of brain-targeted therapies.

Expert opinion: Nanomedicine may be particularly useful in brain drug delivery, mainly due to the possibility of functionalizing nanoparticles to target specific receptors/transporters. Since the BBB is endowed with numerous receptors and transporters responsible for regulating the proper metabolic activity of the brain, their targeting can be a promising bypass strategy to circumvent the hurdle that the BBB represents for brain drug delivery.

KEYWORDS:

• Blood-brain barrier
• central nervous system
• nanotechnology
• receptors
• receptor-mediated transcytosis
• transporters

Article highlights

• The overall structure and physiology of the blood-brain barrier

• The impact the expression of receptors/transporters can have regarding drug delivery

• The impact certain diseases hold on the expression of receptors/transporters

• Nanoparticles as a breakthrough platform to exploit receptors/transporters of the blood-brain barrier

• Studies demonstrating the use of nanoparticles against these receptors/transporters

This box summarizes key points contained in the article.

Acknowledgments

F Sousa and C Martins would like to thank Fundação para a Ciência e Tecnologia for funding the PhD scholarship (grant SFRH/BD/112201/2015 and SFRH/BD/137946/2018, respectively).

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This article is a result of the project NORTE-01-0145-FEDER-000012, supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). This work was financed by FEDER – Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020 – Operacional Programme for Competitiveness and Internationalisation (POCI), Portugal 2020, and by Portuguese funds through FCT – Fundação para a Ciência e a Tecnologia/Ministério da Ciência, Tecnologia e Ensino Superior in the framework of the project ‘Institute for Research and Innovation in Health Sciences’ (POCI- 01-0145-FEDER-007274).