With the addition of PEI, the synthetic protocol is carried out by first mixing mRNA with 2-MeIM, then adding an optimized amount of PEI (Figure ) allowing a 15-minute incubation, mixing in zinc nitrate, and incubating for 2 hours. This approach resembles previously employed one-pot coprecipitation methods with the distinction that PEI is electrostatically complexed with mRNA before ZIF-8 encapsulation, creating a ZIF-8 shell around the mRNA-PEI complex (mRNA-PEI@ZIF-8) (Scheme 1A). By creating an mRNA-PEI complex core, the mRNA is retained in the core while PEI aids in the stability of the ZIF-8 coating, possibly due to its strong binding of Zn ions with uncomplexed or partially complexed PEI.