Abstract

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.

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