Application Of Radioactive,Fluorescent Probe In Molecular And Cellular Imaging

In recent years, nanoprobes have merged as an excellent tool of molecular imaging because of their ability of loading as many small molecular probes as needed to achieve desired signal. Nevertheless, nanoprobes are facing the problems of cell membrane translocation and targeting, besides the difficulty and reproducibility of their fabrications. Self-assembly, a prevalent and important process in nature, provides an easy solution to the above problems. We utilized a biocompatible condensation reaction between1,2-aminothiol group of cysteine and the cyano group of2-cyanobenzothiazole (CBT) which could be controlled by pH, reduction and protease at such low a concentration as micromolar for self-assembly of nanostructures in living cells. We designed Acetyl-Arg-Val-Arg-Arg-Cys(StBu)-Tyr(I-125)-CBT (1) for self-assembling radioactive nanoparticles (l25I-NPs) under the action of furin in living tumor cells. After entering cells, the disulfide bond of the Cys motif of1is reduced by the intracellular glutathione (GSH) and subsequently its RVRR motif is cleaved by furin on site, resulting in the active intermediate1-Core. Two1-Cores condense quickly to yield the amphiphilic dimer (i.e.,1-Dimer) which has a hydrophobic macrocyclic core for self-assembling125I-NPs via π-π stacking among each other. As-formed125I-NPs could concentrate the radioactivity inside cells on one hand. On the other hand, the big size and the hydrophobic nature of the125I-NPs would prevent themselves from being pumped out by the cells. Compared with those control probes (e.g., scrambled control1-Scr) which could not be cleaved by furin or self-assemble in cells,1should have an enhanced cellular uptake by tumor cells, suggesting its promising application on tumor imaging in vivo.Intracellular biothiols, such as cysteine (Cys), homocysteine (Hcy), and glutathione (GSH), play crucial roles in maintaining redox homeostasis in biological systems through equilibrium between the reduced free thiol and oxidized disulfide forms. Generally, alternations in the level of cellular thiols are closely associated with certain diseased states including leucocyte loss, psoriasis, liver damage, cancer, acquired immune deficiency syndrome (AIDS), and cardiovascular diseases. Consequently, assessments of the levels of these mercapto biomolecules in biological systems may aid early diagnoses of some diseases. We rationally designed a sulfonamide-based self-quenched fluorescent probe1whose fluorescence is turned "on" at a maximum of522.517. or490nm upon that addition of Cys. Hcy, or GSH, respectively. Unlike previous sulfonamide-fluorescent probes which are only subjected to biothiol-reductions. fluorescent probe1is subjected to GSH-reduction. Cys-condensation and reduction, Hcy-condensation and reduction to yield respective products of2-cyano-6-aminobenzothiazole (CBT), Aminoluciferin, CBTHcy which have different fluorescent emission maximums. Employing its high sensitivity and good selectivity to GSH. Cys, and Hey, we successfully applied fluorescent probe1for discriminative sensing of these biothiols among the20natural AAs in vitro. Furthermore, fluorescent probe1was also successfully used for discriminative sensing of Cys and GSH in living cells by ratiometric quantification.There is an increasing need for developing new methodologies for quick and specific detection of cadmium ions in vitro and in vivo, as well as for its absorption. Due to inherent good properties (e.g., biocompatibility and biodegradability) as biomaterials, supramolecular hydrogels have attracted broad research interests and been extensively explored in recent years. Hydrogels have recently shown very exciting and promising applications for sensing metal ions or detection of biomarkers.We rationally designed bipyridine-derivatived hydrogelator1for quick and selective detection of Cd2" and absorption. We found that hydrogelator1can selectively and specifically coordinate with Cd2+, turning on its fluorescence emission at470nm (86-fold increase). Interestingly,1.5wt%of this bipyridine derivative1in water at pH5.5self-assembles into nanofibers to form hydrogel and the hydrogel was successfully applied to visibly detect and absorb Cd2+Metal-ligand interactions play an important role in natural biological systems. Over the past decade, coordination-based self-assembly system has evolved into a well-established strategy for constructing novel nanostructures via metal-ligand interactions. Among the metal-ligand interactions, metal-bipyridine coordinations are always employed to assemble building blocks into higher order nanostructures. We rationally designed a bipyridine-derivative1which contains two2-cyano-6-aminobenzothiazole (CBT) motifs and latent cysteine groups for intramolecular macro-cyclization to self-assemble nanorings. A bipyridine motif which links to the side chains of lysine motifs within1was designed for the coordination with metal ions after the formation of the nanorings. In detail. upon tris(2-carboxyethyl)phosphane (TCEP)-reduction, the disulfide bonds of1were cleaved, initiating the intramolecular condensation reaction to yield macrocyclized product3. Then the amphiphilic3instantly self-assembled into nanostructures (herein, nanorings) with abundant bipyridine groups on their surfaces. Upon addition of metal ions (herein, Fe2+), the nanorings were gathered together to form higher order nanostructures via Fe2+-bipyridine coordination.