In-Situ Encapsulation of Protein into Nanoscale Hydrogen-Bonded Organic Frameworks for Intracellular Biocatalysis

Hydrogen-bonded organic frameworks (HOFs) are porous materials with great potential for biological applications. The self-assembly of HOFs and biomacromolecules, however, is challenging. We report herein the self-assembly of nanoscale HOFs (nHOFs) to encapsulate protein for intracellular biocatalysis. The self-assembly of tetrakis(4-amidiniumphenyl)methane and azobenzenedicarboxylate can encapsulate protein in situ to form protein@nHOFs under mild conditions. This strategy is applicable to proteins with different surface charge and molecular weight, showing a high protein encapsulation efficiency and minimal effect on protein activity. A cellular delivery study shows that the protein@TA-HOFs can efficiently enter cells and retain enzyme activity for biochemical catalysis in living cells for neuroprotection. Our strategy paves new avenues for interfacing nHOFs with biological settings and sheds light on expanding nHOFs as a platform for biomacromolecule delivery and disease treatment.