posted on 2020-08-24, 23:03authored byAndrea
N. Trementozzi, Stephanie Hufnagel, Haiyue Xu, Mahmoud S. Hanafy, Felipe Rosero Castro, Hugh D.C. Smyth, Zhengrong Cui, Jeanne C. Stachowiak
Chemotherapeutic
delivery is limited by inefficient transport across
cellular membranes. Here, we harness the cellular gap junction network
to release therapeutic cargos directly into the cytosol. Specifically,
cell-derived vesicles, termed connectosomes, contain gap junction
transmembrane proteins that open a direct passageway to the cellular
interior. Connectosomes were previously shown to substantially improve
chemotherapeutic delivery in vitro. Here, we test
connectosomes in vivo, using a murine breast tumor
model. We demonstrate that connectosomes improve chemotherapeutic
delivery to cellular targets within tumors by up to 16-fold, compared
to conventional drug-loaded liposomes, suggesting an efficient alternative
pathway for intracellular delivery.