Site-Selective Functionalization of Outer Surface and Different Inner Spaces of Nanoscale Hierarchically Mesoporous MOFs for the Specific Detection of Cancer Cells

Spatial functionalization of hierarchically mesoporous metal–organic frameworks (HMMOFs) in a controllable manner is highly desirable yet challenging. Herein, microporous and mesoporous spaces as well as the external surface of nanoscale hierarchically mesoporous UiO-66-NH2 MOFs were site-separately modified to endow them with additional functionalities. Given the pore-filling effect of soft templates, the folic acid ligand was successfully grafted on the outer surface without reducing the pore size and available pore volumes, making the developed sensing nanoprobe competent to specifically identify cancer cells. The mesoporous support not only effectively protected the encapsulated enzymes but also facilitated the proximity between the substrates and enzymes by virtue of the spatial confinement effect. The Cu2+ ions introduced in microporous skeleton could synergistically activate the activity of horseradish peroxidase immobilized in mesopores. Thanks to such enhanced enzymatic activity and spatial functionalities, the designed nanoprobe could specifically and quantitatively check out FR-overexpressed cancer cells in a colorimetric and visible way. Through deliberately screening different functionalities in specific locations of HMMOFs, such a model is expected to set a guideline for the design of multiple-functional diagnostic platform for the detection of various cancers.