WCSS Researchers Developed a Peptide-Based Coacervate Protocell with Cytoprotective Metal-Phenolic Network Membranes as Innovative Targeted Delivery Systems
Journal cover: Peptide-Based Coacervate Protocells with Cytoprotective Metal?Phenolic Network Membranes
A collaborative team of researchers from the West China School of Stomatology (WCSS) and the College of Biomass Science and Engineering at Sichuan University has achieved a significant breakthrough by developing a membranized peptide coacervate (PC) with oppositely charged oligopeptides as the molecularly crowded cytosol and a metal-phenolic network (MPN) coating as the membrane. Their research
Design and fabrication of PC@MPN membrane-bound protocells.
Protocells have garnered considerable attention from various scientific disciplines, including cell biologists, materials scientists, and synthetic biologists. However, the membrane-free nature of such coacervates leads coalescence into a bulk phase, a phenomenon that is not representative of the cells they are designed to mimic.
To overcome this challenge, Researchers fabricated a membrane-bound protocell (PC@MPN) with emergent properties by coating peptide coacervates (PCs), which mimic the cytosol, with MPNs, which serve as cytomembranes. This mild synthesis relies on the liquid-liquid phase separation of oligopeptides and the strong coordination between phenolic ligands and metal ions, creating highly biocompatible and robust membrane-bound protocells. The resultant PC@MPNs allow for a biomolecule-rich interior capable of supporting a series of localized biocatalytic cascade reactions.
Moreover, the semipermeable PC@MPNs possess long-term colloidal stability and the ability to scavenge radicals. Notably, the ability to sequester and maintain the activity of enzymes, tailor the physicochemical properties, and modify the surface, sets a solid foundation for utilizing PC@MPNs as targeted drug delivery systems. Researchers also validated PC@MPNs as delivery platforms for anticancer therapy (e.g., doxorubicin).
In summary, this study reports the development of a novel membrane-bound protocell (PC@MPN) that addresses the limitations of traditional membrane-free protocells, which tend to coalesce and not accurately mimic cellular structures. By combining peptide coacervates with metal-phenolic networks, they've created a biocompatible and robust system with a biomolecule-rich interior ideal for localized biocatalytic reactions. These PC@MPNs are semipermeable, stable, and capable of scavenging radicals, making them promising candidates for targeted drug delivery. The research further demonstrates their potential as vehicles for anticancer agents like doxorubicin, highlighting their application in therapeutic delivery.
Linli Jiang and Yiwei Zeng, both Ph.D. candidates, alongside postdoctoral fellow Hui Li, are acknowledged as co-first authors of the study. Professors Jiajing Zhou from Sichuan University's College of Biomass Science and Engineering, Lei Liu from the hosting institution, and Frank Caruso from the University of Melbourne have been credited as co-corresponding authors.
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