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Connexin-Containing Vesicles for Drug Delivery

  • Review Article
  • Recent Advances in Drug Delivery
  • Published:
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Abstract

Connexin is a transmembrane protein present on the cell membrane of most cell types. Connexins assemble into a hexameric hemichannel known as connexon that pairs with another hemichannel present on a neighboring cell to form gap junction that acts as a channel or pore for the transport of ions and small molecules between the cytoplasm of the two cells. Extracellular vesicles released from connexin-expressing cells could carry connexin hemichannels on their surface and couple with another connexin hemichannel on a distant recipient cell to allow the transfer of the intravesicular content directly into the cytoplasm. Connexin-containing vesicles can be potentially utilized for intracellular drug delivery. In this review, we introduced cell-derived, connexin-containing extracellular vesicles and cell-free connexin-containing liposomes, methods of preparing them, procedures to load cargos in them, factors regulating the connexin hemichannel activity, (potential) applications of connexin-containing vesicles in drug delivery, and finally the challenges and future directions in realizing the promises of this platform delivery system for (intracellular) drug delivery.

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Abbreviations

Cx:

Connexin

GJ:

Gap junction

EVs:

Extracellular vesicles

CL:

Cytoplasmic loop

EC:

Extracellular loop

PMVs:

Plasma membrane vesicles

MVBs:

Multivesicular bodies

GPMVs:

Giant plasma membrane vesicles

NTA:

Nanoparticles tracking analysis

HEK:

Human embryonic kidney

RPE:

Retinal pigmented epithelium

Dio:

Dioctadecyloxacarbocyanine

YFP:

Yellow fluorescent protein

GFP:

Green fluorescent protein

RFP:

Red fluorescent protein

GFPnb:

Green fluorescent protein nanobody

PFA:

Paraformaldehyde

DTT:

Dithiothreitol

NEM:

N-ethylmaleimide

HEPES:

4-(4-Hydroxyethyl)-1-piperazine ethane sulfonic acid

TEM:

Transmission electron microcopy

VEGF:

Vascular endothelial growth factor

EDTA:

Ethylenediaminetetraacetic acid

EGTA:

Ethylene glycol tetra acetic acid

PI:

Propidium iodide

POPC:

1-Palmitoyl-2-oleoyl-snglycero-3-phosphocholine

DOPE:

1,2-Dioleoyl-sn-glycero-3-phosphoethanolamine

TEV:

Tobacco Etch Virus

MAP:

Mitogen-activated protein

GA:

Glycyrrhetinic acid

CBX:

Carbenoxolone

TMZ:

Temezolamide

CFTR:

Cystic fibrosis transmembrane conductance regulator

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  1. Division of Molecular Pharmaceutics and Drug Delivery, College of Pharmacy, The University of Texas at Austin, Austin, Texas, USA

    Mahmoud S. Hanafy & Zhengrong Cui

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Hanafy, M.S., Cui, Z. Connexin-Containing Vesicles for Drug Delivery. AAPS J 26, 20 (2024). https://doi.org/10.1208/s12248-024-00889-8

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