A supramolecular hydrogel 1, prepared at high concentration (5-10 wt%), exhibited mechanical toughness comparable to that of a polymer hydrogel, even though the gel was constructed solely by noncovalent bonding interactions among small molecules. The mechanical toughness and thermal reversibility of gel 1 allowed us to fabricate a supramolecular hydrogel capsule (SH-capsule) 1 which was easily handled and was stable in aqueous and cell culture media. The mechanical and substancerelease/uptake properties of SH-capsule 1 were investigated by atomic force microscope (AFM) indentation, fluorescence spectroscopy, and confocal laser scanning microscopy (CLSM). On the basis of those properties we successfully designed an enzyme-and cell-responsive SH-capsule. To install a function of enzyme-responsive substance release into the SH-capsule 1, enzyme-labile, amphiphilic additive 2 was embedded in supramolecular nanofibers of 1 through a supramolecular co-assembly method. As a proof-of-concept, we constructed the functional SH-capsule 1/2 that can release a model fluorescent drug triggered by prostate specific antigen (PSA)-catalyzed proteolysis. Selective release of the fluorescent substance was exploited to both assay PSA activity and detect prostate cancer (PCa) cells. We also clearly demonstrated that the released fluorescent substance was delivered and internalized into the PCa cells, mediated by binding to the membrane-bound protein prostate-specific membrane antigen (PSMA), which is over-expressed on a plasma membrane of the PCa cells.

The development of protein and sensor arrays is crucial for rapid and high-throughput assays of biological events, markers, environmental pollutants, and others. We describe supramolecular hydrogel as a unique material for use as a matrix for immobilizing proteins, peptides, substrates, chemosensors, and mesoporous silica particles, and thereby array them on solid supports. The semi-wet conditions provided by the gel, which consists of 3D supramolecular nanofiber network structure, are suitable for entrapping such substances whilst retaining their activity and function. Moreover, the hydrophobic interior of the nanofibers of the supramolecular hydrogel can reversibly entrap hydrophobic molecules, which allows the development of various read-out systems, such as fluorescence enhancement and fluorescence resonance energy transfer (FRET), by which one can monitor the signal changes associated with, for instance, molecular recognition and enzyme activity.

We developed supramolecular hydrogels exhibiting reversible thermochromism concurrently with gel-to-sol transition from four glycolipids. In addition, these gels showed the similar color change in response to glycosidases, which can be employed to construct a colorimetric sensor array chip for sensing glycosidases with the naked eye.