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