Green Route to Prepare Biocompatible and Near Infrared Thiolate-Protected Copper Nanoclusters for Cellular Imaging

Abstract

Ultra-small and functional copper nanoclusters (Cu NCs) have been extensively used in consumer technologies due to their superior properties. A simple and green way to prepare stable, watersoluble and near-infrared (NIR) Cu NCs by using a reducing agent was reported in this work. Reduced glutathione (GSH) worked as an important sca®old to prevent NCs from aggregating. Since GSH has functional groups such as carboxyl and amino, it can also be used in reducing Cu 2þ ions. The resulting GSHÀCu NCs with a particle size of 2.5 nm have good dispersibility in aqueous solution, and show NIR emission with a wavelength of 700 nm (quantum yield 0.6%). MC3T3-E1 cells are used as an example in the°uorescence imaging of GSHÀCu NCs. Several promising features including NIR°uorescence, good water-solubility and biocompatibility, bioactive surface and ultra-small size make the GSHÀCu NCs a good probe for cells.

Different Color Emissive Copper Nanoclusters for Cancer Cell Imaging

“…FEG‐TEM studies of blue CuNCs (Figure ) demonstrate that most of the blue CuNCs have a size of 1.7 nm (Figure ). This value is comparable with the size of CuNCs reported previously by other research groups . It has also been shown from theoretical study that copper nanoclusters show drastic variation in band gap within the size limit 2–6 nm (typical behavior of quantum dots) and above 12 nm they behave like bulk copper .…”

“…In all cases the metal precursor was copper acetate monohydrate [Cu(OAc) 2 , H 2 O] and for stabilizing the nanoclusters reduced glutathione (GSH) was used (see Table S1 of Supporting Information). Many other groups have successfully used glutathione as a stabilizing agent; they have maintained a basic pH to synthesize the desired nanoclusters . However, in this study we have maintained almost neutral or physiological pH (7.46) to maximize the use of CuNCs as biomaterials in future.…”

“…Quantum yields of blue, cyan and green emitting CuNCs have been found to be 1.24, 1.27 and 0.438 %. It has been shown previously that nanoclusters stabilized with small ligands in aqueous medium generally show lower quantum yield values compared to the nanoclusters stabilized with macromolecules, for example, proteins and synthetic polymers . This probably happens due to dissipation of fluorescence excited state energy by non‐radiative pathways …”

“…Most of these studies include emission color tuning in a very narrow range ,. Moreover, it is worth to mention that most of the CuNCs have been synthesized at very high pH range and by using various organic solvents and this is not desirable for biological applications of these nanomaterials ,. Therefore, it is important to prepare multiple color emissive CuNCs in water with neutral or physiological pH.…”

Glutathione-stabilized Cu nanoclusters as fluorescent probes for sensing pH and vitamin B1

“…Compared to the previously reported protocol [38], the current synthesis method showed obvious superiority. First, the synthesis procedure was performed at the physiological temperature (37 ), and the reaction has been completed within 1h.…”