Self-assembling nanocarriers from engineered proteins: Design, functionalization, and application for drug delivery

Self-assembling proteins are valuable building blocks for constructing drug nanocarriers due to their self-assembly behavior, monodispersity, biocompatibility, and biodegradability. Genetic and chemical modifications allow for modular design of protein nanocarriers with effective drug encapsulation, targetability, stimuli responsiveness, and in vivo half-life. Protein nanocarriers have been developed to deliver various therapeutic molecules including small molecules, proteins, and nucleic acids with proven in vitro and in vivo efficacy. This article reviews recent advances in protein nanocarriers that are not derived from natural protein nanostructures, such as protein cages or virus like particles. The protein nanocarriers described here are self-assembled from rationally or de novo designed recombinant proteins, as well as recombinant proteins complexed with other biomolecules, presenting properties that are unique from those of natural protein carriers. Design, functionalization, and therapeutic application of protein nanocarriers will be discussed. (C) 2022 Elsevier B.V. All rights reserved.