The Display of Single-Domain Antibodies on the Surfaces of Connectosomes Enables Gap Junction-Mediated Drug Delivery to Specific Cell Populations.

Abstract:

:Gap junctions, transmembrane protein channels that directly connect the cytoplasm of neighboring cells and enable the exchange of molecules between cells, are a promising new frontier for therapeutic delivery. Specifically, cell-derived lipid vesicles that contain functional gap junction channels, termed Connectosomes, have recently been demonstrated to substantially increase the effectiveness of small molecule chemotherapeutics. However, because gap junctions are present in nearly all tissues, Connectosomes have no intrinsic ability to target specific cell types, which potentially limits their therapeutic effectiveness. To address this challenge, here we display targeting ligands consisting of single-domain antibodies on the surfaces of Connectosomes. We demonstrate that these targeted Connectosomes selectively interact with cells that express a model receptor, promoting the selective delivery of the chemotherapeutic doxorubicin to this target cell population. More generally, our approach has the potential to boost cytoplasmic delivery of diverse therapeutic molecules to specific cell populations while protecting off-target cells, a critical step toward realizing the therapeutic potential of gap junctions.

journal_name

Biochemistry

journal_title

Biochemistry

authors

Gadok AK,Zhao C,Meriwether AI,Ferrati S,Rowley TG,Zoldan J,Smyth HDC,Stachowiak JC

doi

10.1021/acs.biochem.7b00688

subject

Has Abstract

pub_date

2018-01-09 00:00:00

pages

81-90

issue

1

eissn

0006-2960

issn

1520-4995

journal_volume

57

pub_type

杂志文章