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Connectosomes deliver drugs straight to the cytoplasm

Transport via cell-derived lipid vesicles with built-in channels decreases the necessary dose of cancer drug by at least an order of magnitude

by Celia Henry Arnaud
October 3, 2016 | A version of this story appeared in Volume 94, Issue 39

Encasing drugs in nanoparticles can help get them across cell membranes. But because cells often take up such nanoparticles via endocytosis, the drugs can end up trapped in endosomes. Biomedical engineering professor Jeanne C. Stachowiak, grad student Avinash K. Gadok, and coworkers at the University of Texas, Austin, bypass this problem by using structures called connectosomes to deliver drugs straight into the cytoplasm (J. Am. Chem. Soc. 2016, DOI: 10.1021/jacs.6b05191). The lipid membranes of these connectosomes are densely populated with gap junctions, channels for exchanging molecules between cells. The researchers harvest the connectosomes from the plasma membranes of donor cells engineered to produce a large number of connexins, the proteins that make up gap junctions. The researchers can load drugs into the donor cells so the drugs are encapsulated as the connectosomes form. Alternatively, they can incubate the connectosomes in a solution of the desired cargo. In cell assays, connectosomes reduced the necessary dose of the anticancer drug doxorubicin by about one order of magnitude compared with free doxorubicin and by several orders of magnitude compared with doxorubicin encapsulated in conventional liposomes.

Schematic showing the formation of connectosomes.
Credit: J. Am. Chem. Soc.
Connectosomes are formed by blebbing them from the membranes of cells that are engineered to produce a large number of gap junctions (green).


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