Engineering protein nanocages as carriers for biomedical applications

This is the authors' abstract. We don't add key points for this paper.

Protein nanocages have been explored as potential carriers in biomedicine. Formed by the self-assembly of protein subunits, the caged structure has three surfaces that can be engineered: the interior, the exterior and the intersubunit. Therapeutic and diagnostic molecules have been loaded in the interior of nanocages, while their external surfaces have been engineered to enhance their biocompatibility and targeting abilities. Modifications of the intersubunit interactions have been shown to modulate the self-assembly profile with implications for tuning the molecular release. We review natural and synthetic protein nanocages that have been modified using chemical and genetic engineering techniques to impart non-natural functions that are responsive to the complex cellular microenvironment of malignant cells while delivering molecular cargos with improved efficiencies and minimal toxicity. Researchers have identified three components of self-assembled protein nanocages (PNCs)that can be engineered to improve delivery of molecular cargos. Biological systems such as virus capsids and the protein ferritin have cage-like structures and membrane-permeating capabilities that make them natural platform candidates for transporting molecules directly to cells. Sierin Lim and her team from Nanyang Technological University in Singapore survey progress in modifying PNCs interiors to improve drug loading, exteriors to enhance biocompatibility and display of ligands, and interactions between subunits to tune molecular release. Hybrid nanostructures that combine protein scaffolds with synthetic components, such as thermoresponsive polymers, are helping to impart additional functions to the PNCs. The authors foresee PNCs that combine multiple functionalities on a single platform and their development as agents in immunotherapy and immunoengineering as future directions for the field. Formed by the self-assembly of protein subunits, protein nanocages can be engineered at the interior, exterior, and inter-subunit locations. Each type of modification can be tuned for specific biological applications. Multiple-modifications can be imparted to these nanocages without compromising its self-assembling property, creating multi-functional protein nanocage platforms. Potential applications of the modified protein nanocages include targeted delivery in complex cellular environments for therapeutic and diagnostic agents as well as modulation of cellular responses.