By employing fluorescence resonance energy transfer (FRET) quenching, we rationally designed two new FITC-quencher based nanoprobes for effectively sensing caspase 3 (Casp3) in vitro and in cells. Our nanoprobes hold promise for assessing the chemotherapeutic effect of cancer treatment.
Alkaline phosphatase (ALP) is an important enzyme, but direct imaging of ALP activity with high spatiotemporal resolution remains challenging. In this work, we rationally designed an iodinated hydrogelator precursor Nap-Phe-Phe(I)-Tyr(HPO)-OH (1P) which self-assembles into nanofibers to form hydrogel under the catalysis of ALP. With this property of concentrating iodine atoms at the locations of ALP, 1P was successfully applied for direct nanocomputed tomography (nano-CT) imaging of ALP activity in bacteria for the first time. We envision that, on the basis of this pioneering work, new hydrogelators containing more iodine atoms (e.g., five iodine atoms in 1P) will be designed for better nano-CT imaging of ALP activity with higher CT contrast in the near future.
Herein, we report, for the first time, the use of MRI methods to study enzymatic hydrogelation. Supramolecular hydrogels have been exploited as biomaterials for many applications. However, behaviors of the water molecules encapsulated in hydrogels have not been fully understood. In this work, we designed a precursor 1 which could self-assemble into nanofibers and form hydrogel I (gel I) upon the catalysis of phosphatase. The differences of mechanic property, pore size, water diffusion rate, and magnetic resonance relaxation times T1 and T2 of gel I containing different concentrations of 1 were systematically studied and analyzed. T1, T2, and diffusion-weighted (1)H MR images from gel I phantoms were obtained at 9.4 T. Analyses of the MRI data uncovered how the density of the nanofiber networks affects the relaxation behaviors of the water protons encapsulated in such hydrogels. Rheological analyses and cryo-TEM observations showed increased gel elasticities with increased concentrations of 1 while the pore sizes of gel I decreased. This also resulted in an increase in the proton relaxation rate (i.e., shortened T1, T2, and apparent diffusion coefficient (ADC)) for the water encapsulated in the hydrogel. With MRI, our study provides a new in vitro method to potentially mimic and study in vivo diseases that involve fibrous aggregates.
Osteoporosis (OP) is an important aging-related disease and the effective prevention/treatment of this disease remains challenging. Considering the acidic microenvironment of bone resorption lacunae, herein, we rationally designed two pamidronate (Pami)-derivative and alendronate (Alen)-derivative hydrogelators and which self-assemble into nanofibers to form supramolecular hydrogels under acidic conditions. Cell viability assay, osteoclastogenesis, osteoclastic gene expression, and in vitro bone resorption results indicated that both and have better inhibitory effects on osteoclastic formation and bone resorption than Pami and Alen, respectively. We anticipate that our new drugs and could "smartly" self-assemble and locally concentrate the drugs at bone resorption lacunae in vivo and subsequently prevent/treat osteoporosis more efficiently.
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