Gap Junction Liposomes for Efficient Delivery of Chemotherapeutics to Solid Tumors

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.