Modulation of coacervate coarsening in liquid-liquid phase separation (LLPS)

Abstract

From the Humboldt squid beak proteins, pH responsive self-coacervating peptides were developed as a novel drug delivery system. These peptides are capable of sequestering and releasing cargos, hinting at their biomedical applications. While coacervates are readily internalised by cells, coacervates generally have a hydrodynamic diameter in the range of micrometres. To enable passive targeting of tumours using coacervates requires the understanding of factors affecting coacervate size. In this study, dynamic light scattering (DLS) was used to determine the effect of molecular crowders, bovine serum albumin (BSA) and tocopherol glycerol succinate (TPGS), on GW26 coacervate size, with and without sequestered proteins. Time dependency studies were conducted to understand GW26 coacervate stability over time. Finally, cellular uptake of size modified, protein sequestered GW26 was conducted, showing little effect of coacervate size on GW26 uptake. These results improved our understanding of coacervate size control, enabling potential use as a passively targeting drug delivery system via enhanced permeation and retention effect.