Taking advantage of cellular uptake of ferritin nanocages for targeted drug delivery

Abstract The search for ideal nanocarrier, which could be rapidly translated to clinical practice, is still ongoing over the past few decades. However, many reviews are focused on important properties of ideal nanocarrier, including long circulation, high internalization efficiency of a drug, surface charge of nanocarrier or the ability to encapsulate high amount of a drug. Indeed, the ability to encapsulate wide variety of drugs, no immunogenicity, biodegradability or nanocarrier monodispersity are very important aspects, therefore they are discussed in this review. The use of nanocarrier formulations able to innately form self-assembly cages of uniform size and shape, employing protein-based structures naturally present in human body, seems to be very promising. Typical protein nanocarrier disposing all the above mentioned characteristics is represented by ferritin (FRT). Hence, the presented review provides detailed characterization of FRT structure, including its disassembly and reassembly properties, which are crucial for encapsulation of drugs, together with possibilities of active targeting, exploiting both the innate affinities of FRT nanocages towards selected receptors and the plethora of surface functional groups that can be used to attach a variety of targeting ligands. Finally, we discuss the opportunities of cutting-edge approaches to FRT-based nanotherapy and the challenges that must be overcome or avoided.