Ferritin - a multifaceted protein scaffold for biotherapeutics

Abstract

The ferritin nanocage is an endogenous protein that exists in almost all mammals. Its hollow spherical structure that naturally stores iron ions has been diversely exploited by researchers in biotherapeutics. Ferritin has excellent biosafety profiles, and the nanosized particles exhibit rapid dispersion and controlled/sustained release pharmacokinetics. Moreover, the large surface-to-volume ratio and the disassembly/reassembly behavior of the 24 monomer subunits into a sphere allow diverse modifications by chemical and genetic methods on the surface and inner cage of ferritin. Here, we critically review ferritin and its applications. We (i) introduce the application of ferritin in drug delivery; (ii) present an overview of the use of ferritin in imaging and diagnosis for biomedical purposes; (iii) discuss ferritin-based vaccines; and (iv) review ferritin-based agents currently in clinical trials. Although there are no currently approved drugs based on ferritin, this multifunctional protein scaffold shows immense potential in drug development in diverse categories, and ferritin-based drugs have recently entered phase I clinical trials. This golden shortlist of recent developments will be of immediate benefit and interest to researchers studying ferritin and other protein-based biotherapeutics. Ferritin: Delivering more than just iron Ferritin molecules, hollow protein spheres that store and release iron as needed, also hold promise for disease diagnosis, drug delivery, and vaccine development. Almost all organisms produce ferritin, which consists of 24 protein subunits that can interact with metals. Its biocompatibility, large surface-to-volume ratio, and ease of modification have led to investigation of its use in various medical applications, as reviewed by In-San Kim at the Korea Institute of Science and Technology in Seoul, South Korea, and co-workers. Ferritin can rapidly disperse, and release its contents steadily over a long time. It can deliver diagnostic imaging compounds or drugs to specific cells, or display antigens for immunotherapy or vaccines. Testing is underway for ferritin-based delivery of cancer drugs and development of vaccines for influenza, SARS-CoV-2, and diseases associated with Epstein Barr virus.