SCIENCE@home

LRP-1-mediated intracellular antibody delivery to the Central Nervous System

Xiaohe Tian,S. Nyberg,P. Sharp,J. Madsen,Nooshin Daneshpour,S. Armes,J. Berwick,M. Azzouz,P. Shaw,N. Joan Abbott,G. Battaglia

Published 2015 in Scientific Reports

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.

PUBLICATION RECORD

CITATION MAP

EXTRACTION MAP

CLAIMS

  • No claims are published for this paper.

CONCEPTS

  • No concepts are published for this paper.

REFERENCES

Showing 1-51 of 51 references · Page 1 of 1

CITED BY

Showing 1-100 of 146 citing papers · Page 1 of 2

12
Next