An international collaboration between researchers at The Centre for Programmable Matter at Durham University (U.K.) and the Malopolska Centre of Biotechnology, Jagiellonian University (Poland) has resulted in the generation of a novel artificial protein cage that holds great promise as an advanced drug delivery system, according to the scientists, who reported their study “Designed, Programmable Protein Cages Utilizing Diverse Metal Coordination Geometries Show Reversible, pH-Dependent Assembly” in Macromolecular Rapid Communications.
The team says it has crafted a highly adaptable artificial protein cage, based on a ring-shaped scaffold made of TRAP proteins. These nano-scale structures feature strategically positioned metal-binding sites that enable self-assembly into highly organized structures upon exposure to cobalt or zinc ions. These cages have the potential to carry therapeutic cargo in their hollow core.
Most importantly, although highly stable, the cages can be triggered to open up and free their cargoes in certain disease-specific conditions. These include changes in pH, such as those associated with some cancers.
“The rational design and production of a novel series of engineered protein cages are presented, which have emerged as versatile and adaptable platforms with significant applications in biomedicine. These protein cages are assembled from multiple protein subunits, and precise control over their interactions is crucial for regulating assembly and disassembly, such as the on-demand release of encapsulated therapeutic agents,” write the investigators.
“This approach employs a homo-undecameric, ring-shaped protein scaffold with strategically positioned metal binding sites. These engineered proteins can self-assemble into highly stable cages in the presence of cobalt or zinc ions. Furthermore, the cages can be disassembled on demand by employing external triggers such as chelating agents and changes in pH. Interestingly, for certain triggers, the disassembly process is reversible, allowing the cages to reassemble upon reversal or outcompeting of triggering conditions/agents.
“This work offers a promising platform for the development of advanced drug delivery systems and other biomedical applications.”