Smart nanosized materials with high stability, suitable pharmacokinetics and efficient cell permeability for delivering cargo molecules to target cells have been the requirements for an ideal drug delivery system. Advances in the design and fabrication of synthetic carriers such as cationic liposomes, micelles, block copolymers, carbon nanotubes, dendrimers and inorganic nanoparticles are restricted by severe toxicity and low delivery efficiency. Nature-derived nanocarriers are potential alternatives to synthetic ones as they satisfy most of the key features, such as biocompatibility Examples of nature-derived nanocarriers include protein nanocages such as viruses, ferritin and many others that are formed by the self-assembly of protein subunits, resulting in a cage-like structure. The monodispersed subunits are modifiable through chemical a Specific functional polypeptides can be modified to self-assemble into nanoparticles with or without caged structures with desirable nanoscale properties in terms of size and geometry. The assembly of the functional building blocks to form protein nanoparticles, as observed in natural viruses, can seldom be mimicked by general nanofabrication techniques nd genetic methods.

Among myriad nature-derived nanocarriers, protein-based biological systems such as viruses have been a subject of intense study owing to their innate ability to penetrate cell membranes. The structure of viruses best represents the principles of protein assembly in nature. Structural analyses of viruses show that they consist of a protein shell comprising a definite number of subunits that surrounds and protects its genome. Viral capsids are naturally programmed for host-cell targeting and cell entry. They have evolved to mediate the exchange of nucleic acids between different chemical environments. Here you can see the cryoEM structure of an ultra-stable artificial protein cage, the assembly and disassembly of which can be controlled by metal coordination at the protein-protein interfaces. In the presence of Gold atoms, that act as staples, the protein nanocage is formed by the spherical arrangement of protein monomers. The nanocage structure could be destroyed by reducing agents in a reversible process that can be very useful for the encapsulation of active compounds (PDB code: 6RVV)