Phase-Separated Coacervates of Low-Molecular-Weight Compounds for Cytosolic Delivery and Disease Treatment

Liquid-liquid phase separation (LLPS)-driven coacervate droplets, formed by the self-assembly of phase-separating molecules, have emerged as a new platform for the intracellular delivery of macromolecular therapeutics such as antibodies, plasmids, and mRNA. Their appeal lies in their high loading capacity, low cytotoxicity, and high cellular uptake efficiency. Beyond traditional polymer and protein systems, recent advances have demonstrated that low-molecular-weight compounds, including peptides and small molecules, can also form functional coacervates. In this perspective, we will discuss and elucidate the possible mechanisms underlying coacervate cellular uptake and highlight their applications in macromolecular delivery and disease therapy. We also provide our perspective on future research directions and translational opportunities. By critically evaluating these aspects, we aim to bridge fundamental insights with translational potential while providing a promising strategy in disease treatment.