High-Yield Separation of Extracellular Vesicles Using Programmable Zwitterionic Coacervates.

Programmable coacervates based on zwitterionic polymers are designed as dynamic materials for ion exchange bioseparation. These coacervates are proposed as promising materials for the purification of soft nanoparticles such as liposomes and extracellular vesicles (EVs). It is shown that the stimulus-responsiveness of the coacervates and the recruitment of desired molecules can be independently programmed by polymer design. Moreover, the polymeric coacervates can recruit and release intact liposomes, human EVs, and nanoalgosomes in high yields and separate vesicles from different types of impurities, including proteins and nucleic acids. This approach combines the speed and simplicity of precipitation methods and the programmability of chromatography with the gentleness of aqueous two-phase separation, thereby guaranteeing product stability. This material represents a promising alternative for providing a low-shear, gentle, and selective purification method for EVs.

Intracellular delivery of therapeutic proteins. New advancements and future directions.

Achieving the full potential of therapeutic proteins to access and target intracellular receptors will have enormous benefits in advancing human health and fighting disease. Existing strategies for intracellular protein delivery, such as chemical modification and nanocarrier-based protein delivery approaches, have shown promise but with limited efficiency and safety concerns. The development of more effective and versatile delivery tools is crucial for the safe and effective use of protein drugs. Nanosystems that can trigger endocytosis and endosomal disruption, or directly deliver proteins into the cytosol, are essential for successful therapeutic effects. This article aims to provide a brief overview of the current methods for intracellular protein delivery to mammalian cells, highlighting current challenges, new developments, and future research opportunities.