# Metal Nanozymes: New Horizons in Cellular Homeostasis Regulation
## 6 Metal Nanozymes as Cellular Probes for Biosensing
Thus, the ability of nanoceria to oxidize ampliflu to a stable fluorescent product in the pH range 6\(-\)8 was used to develop a sensitive cell-based ELISA at neutral pH without the use of H\({}_{2}\)O\({}_{2}\). In recent years, the ratiometric fluorescence sensors have gained popularity due to their ability to autoclibrate to correct the signal, allowing for more reliable detection [157; 158]. The work of [PERSON] et al. [159] describes a solution slightly different from these classic examples but due to its specific design allowing cellular imaging. The authors have reported an example of using nanozoolitic imidazolate framework (ZIFs), ZIF-90, self-assembled from Zn\({}^{2+}\) and imidazole-2-carboxyaldehyde, to target subcellular mitochondria and image dynamics of mitochondrial ATP in live cells by fluoroscopy. Rhodamine B (RhB) loading into ZIF-90 suppressed the emission of RhB, while the competitive coordination between ATP and the metal node of ZIF-90 dissembled ZIFs, resulting in the release of RhB for fluorimetric ATP sensing. This allowed cellular imaging of the mitochondrial ATP and fluctuations in ATP levels in the processes of cell glycolysis and apoptosis. It should not be forgotten that metal-based nanoparticles, apart from their redox activities, very often consist of an excellent contrast agent in magnetic resonance imaging (MRI). Of particular interest are multimodal MOF-based platforms, such as those described by [PERSON] et al. [128]. An intelligent theranostic nanoplatform based on nanovalve operated metal-organic framework (MOF) core-shell hybrids, incorporating tumorous microenvironment-triggered drug release, MRI, and effective chemotherapy in one pot was reported. This complex structure was based on the Fe\({}_{3}\)O\({}_{4}\) core, covered by the UiO-66 an archetypal Zr-based MOF with a very high surface area. Due to its high thermal stability, tunability, and functionality, UiO-66 has gained scientific popularity over the last decade [160]. Thus, the mentioned multimodal core/shell NPs were further loaded with 5-fluorouracil (5 FU) and equipped with the so-called stalk components binding pillareene-based nanovalves via host-guest binding. This arrangement allowed the multistimuli responsive drug release. In acidic extracellular microenvironments of cancer cells, the host-guest interaction between a nanovalve and a stalk could be broken, causing the turn-on of the nanovalve and subsequent release of cytostatic 5 FU loaded in the as-prepared core-shell nanoplatform. Consequently, the release rate increased with the decrease in pH, at pH 5.0, achieving approximately two times faster rate than in pH 7.0. Furthermore, abnormal ion content caused by pathological changes was also shown to trigger dissociation of the nanovalve and release the drug load. This renders the obtained nanoplatforms useful in the treatment of medical conditions characterized by disrupted ion levels, such as the increased Zn\({}^{2+}\) concentration in the central nervous system and Ca\({}^{2+}\) dyshomeostasis in related bone diseases. The host-guest interaction was also shown to be weakened as temperature increased, giving prerequisites for photothermal therapy (PTT) [128]. A promising direction in biosensing is connected to modification of the metal-based NPs allowing their selective affinity towards important macromolecular biomarkers, such as nucleic acids [161; 162; 163] and peptides [164]. Over the past few decades, electrochemical biosensors have been successfully used to detect a wide variety of molecular and cellular biomarkers. Most importantly, the electrochemical detection system is susceptible to miniaturization and offers advantages such as simplicity, cost-effectiveness, and high sensitivity and specificity [165]. Tunable electrochemical biosensors based on analogous Zr-MOFs were developed for protein detection, the performances of which rely on the pore sizes and surroundings of the MOFs that show diverse binding behaviors to aptamers and then the targeted proteins [166].