Engineering encapsulin nanocages for drug delivery

Encapsulins are a widely distributed and functionally diverse class of protein compartments found across diverse bacterial and archaeal phyla involved in various aspects of microbial metabolism. They self-assemble into cargo-loaded protein shells between ca. 20 and 50 nm in diameter with either T = 1, T = 3 or T = 4 icosahedral symmetry. Encapsulin nanocages possess several key features that make them an attractive engineering platform for creating nanocarrier-based drug delivery systems. This includes a modular and efficient cargo loading mechanism for the facile encapsulation of proteins of interest, diverse physicochemical characteristics and high stability, and robust genetic and chemical strategies of shell modification. For these reasons, encapsulins have garnered significant interest as platforms for various engineering ventures in biomedicine and biotechnology. In this review, we summarize recent advances in engineering encapsulins for drug delivery applications, highlighting their engineerability as a platform technology, innovative strategies employed to enhance their therapeutic potential, and recent concrete drug delivery applications based on engineered encapsulin nanocarriers.