We report for the
first time the controlled drug release
from a
nanoscale Zr-based metal–organic framework (MOF), UiO-66, in
the presence of the enzyme alkaline phosphatase (ALP). This unprecedented
reactivity was possible thanks to the prior functionalization of the
MOF with N3–PEG–PO3ligands, which
were designed for three specific aims: (1) to impart colloidal stability
in phosphate-containing media; (2) to endow the MOF with multifunctionality
thanks to azide groups for the covalent attachment of an imaging agent
by click-chemistry; and (3) to confer stimuli-responsive properties,
specifically the selective release of doxorubicin triggered by the
enzymatic activity of ALP. Cell studies revealed that the functionalization
of the MOF with N3–(PEG)20–PO3ligands improved their intracellular stability and led to
a sustained drug release compared to the bare MOF. More importantly,
an enhanced drug release was observed in cells with higher expression
of ALP genes (HeLa versus MDA-MB-231 and MCF7), confirming the ALP-responsiveness
of the system inside living cells.