Tian, X;
Nyberg, S;
S Sharp, P;
Madsen, J;
Daneshpour, N;
Armes, SP;
Berwick, J;
... Battaglia, G; + view all
(2015)
LRP-1-mediated intracellular antibody delivery to the Central Nervous System.
Scientific Reports
, 5
, Article 11990. 10.1038/srep11990.
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Abstract
The blood-brain barrier (BBB) is by far the most important target in developing new approaches to improve delivery of drugs and diagnostic tools into the Central Nervous System (CNS). Here we report the engineering of pH- sensitive polymersomes (synthetic vesicles formed by amphiphilic copolymers) that exploit endogenous transport mechanisms to traverse the BBB, enabling delivery of large macromolecules into both the CNS parenchyma and CNS cells. We achieve this by targeting the Low Density Lipoprotein Receptor-Related Protein 1 (LRP-1) receptor. We show that LRP-1 is associated with endothelial transcytosis that does not involve acidification of cargo in membrane-trafficking organelles. By contrast, this receptor is also associated with traditional endocytosis in CNS cells, thus aiding the delivery of relevant cargo within their cytosol. We prove this using IgG as a model cargo, thus demonstrating that the combination of appropriate targeting combined with pH-sensitive polymersomes enables the efficient delivery of macromolecules into CNS cells.
| Type: | Article |
|---|---|
| Title: | LRP-1-mediated intracellular antibody delivery to the Central Nervous System |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/srep11990 |
| Publisher version: | http://dx.doi.org/10.1038/srep11990 |
| Language: | English |
| Additional information: | This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > UCL BEAMS UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences > Dept of Chemistry |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1472633 |
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