Engineering protein nanocages as carriers for biomedical applications

Bhaskar, Sathyamoorthy; Lim, Sierin

Protein nanocages are a versatile platform for biomedical applications. The main advantage of protein nanocages is the spatial control of functional groups displayed at well-defined locations through genetic or chemical modifications. To date, only a few nanoplatforms provide for the ability to simultaneously tune size, shape and biocompatibility. Protein nanocages have been shown to be amenable to engineering to cater to specific functions. Despite the multitude of functionalities, the detailed mechanisms for the uptake of the protein nanocages and their intracellular fates are not fully understood. Although cells internalize some of the carrier molecules, the efficiency of delivery to the intended intracellular compartment remains a challenge. Decorating protein nanocages with ligands, such as cell-penetrating peptides, appears to improve the delivery of drug cargos into the cells via nonspecific cellular uptake. To improve the selectivity and enhance local accumulation on target cells, targeting agents have been displayed on the external surface of protein scaffolds.