Coordination-based self-assembled capsules (SACs) for protein, CRISPR-Cas9, DNA and RNA delivery

Biologics, such as functional proteins and nucleic acids, have recently dominated the drug market and comprise seven out of the top 10 best-selling drugs. Biologics are usually polar, heat sensitive, membrane impermeable and subject to enzymatic degradation and thus require systemic routes of administration and delivery. Coordination-based delivery vehicles, which include nanosized extended metal-organic frameworks (nMOFs) and discrete coordination cages, have gained a lot of attention because of their remarkable biocompatibility, in vivo stability, on-demand biodegradability, high encapsulation efficiency, easy surface modification and moderate synthetic conditions. Consequently, these systems have been extensively utilized as carriers of biomacromolecules for biomedical applications. This review summarizes the recent applications of nMOFs and coordination cages for protein, CRISPR-Cas9, DNA and RNA delivery. We also highlight the progress and challenges of coordination-based platforms as a promising approach towards clinical biomacromolecule delivery and discuss integral future research directions and applications.