Biofunctional coacervate-based artificial protocells with membrane-like and cytoplasm-like structures for the treatment of persistent hyperuricemia

Coacervate droplets formed by liquid-liquid phase separation have attracted considerable attention due to their ability to enrich biomacromolecules while preserving their bioactivities. However, there are challenges to develop coacervate droplets as delivery vesicles for therapeutics resulting from the lack of physiological stability and inherent lack of membranes in coacervate droplets. Herein, polylysine-polynucleotide complex coacervate droplets with favorable physiological stability are formulated to efficiently and facilely concentrate small molecules, biomacromolecules and nanoparticles without organic solvents. To improve the biocompatibility, the PEGylated phospholipid membrane is further coated on the surface of the coacervate droplets to prepare coacervate-based artificial protocells (ArtPC) with membrane-like and cytoplasm-like structures. The ArtPC can confine the cyclic catalytic system of uricase and catalase inside to degrade uric acid and deplete the toxicity of H2O2. This biofunctional ArtPC effectively reduces blood uric acid levels and prevents renal injuries in mice with persistent hyperuricemia. The ArtPC-based therapy can bridge the disciplines of synthetic biology, pharmaceutics and therapeutics.

Automated summary

Coacervate droplets formed through liquid-liquid phase separation have potential as delivery vesicles for therapeutics. However, their lack of physiological stability and membranes are challenges. In this study, polylysine-polynucleotide complex coacervate droplets with favorable stability were formulated to concentrate molecules and nanoparticles. Phospholipid membranes were further coated on the droplets to create coacervate-based artificial protocells (ArtPC) with membrane-like structures. These biofunctional ArtPC effectively reduced blood uric acid levels and prevented renal injuries.