Coacervate vesicles assembled by liquid–liquid phase separation improve delivery of biopharmaceuticals

Abstract

Vesicles play critical roles in cellular materials storage and signal transportation, even in the formation of organelles and cells. Natural vesicles are composed of a lipid layer that forms a membrane for the enclosure of substances inside. Here we report a coacervate vesicle formed by the liquid–liquid phase separation of cholesterol-modified DNA and histones. Unlike a phospholipid-based membrane-bounded vesicle, a coacervate vesicle lacks a membrane structure on the surface and is organized with a high-density liquid layer and a water-filled cavity. Through a straightforward coacervation process, we demonstrate that various biological agents, including virus particles, mRNA, cytokines and peptides, can be innocuously and directly enriched in the liquid phase. In contrast to the droplet-like coacervates that are prone to aggregation challenges, coacervate vesicles display superior kinetic stability, positioning them as a versatile delivery vehicle for biopharmaceuticals. We validate that incorporating oncolytic viruses into these coacervate vesicles endows them with potent oncolytic efficacy and elicits robust anti-tumour immune responses in mouse models.