Chitosan-Stabilized Self-Assembled Fluorescent Gold Nanoclusters for Cell Imaging and Biodistribution in Vivo

Abstract

Biocompatible, near-infrared luminescent gold nanoclusters were synthesized in situ using as-prepared chitosan grafted with N-acetyl-l-cysteine (NAC-CS). The fluorescent gold nanoclusters coated with chitosan-N-acetyl-l-cysteine (AuNCs@NAC-CS) were aggregated by multiple ultrasmall gold nanoclusters closing with each other, with strong fluorescence emission at 680 nm upon excitation at 360 nm. AuNCs@NAC-CS did not display any appreciable cytotoxicity on cells even at a concentration of 1.0 mg mL–1. AuNCs@NAC-CS were more insensitive to H2O2 and trypsin compared with fluorescent gold nanoclusters coated with Albumin Bovine V (AuNCs@BSA), which make them have long time imaging in HeLa cells. Furthermore, the obvious fluorescence signal of AuNCs@NAC-CS appeared in the liver and kidney of the normal mice after 6 h injection. And the fluorescence intensity decreased after that because of the highly efficient clearance characteristics of ultrasmall nanoparticles. These findings demonstrated that AuNCs@NAC-CS possessed good fluorescence, low cytotoxicity, and low sensitivity to some content of cells, allowing imaging of the living cells.

Luminescent gold nanoclusters for bioimaging applications

“…Duan et al reported the synthesis of NIR-luminescent AuNCs capped with N-acetyl-ʟ-cysteine (NAC-CS) for longtime imaging[92]. The Au-NAC-CS NCs were insensitive to hydrogen peroxide and trypsin in contrast to Au NCs coated with BSA or other proteins, allowing for extended imaging times in HeLa cells (Figure 6A).…”

Shining Light on Chitosan: A Review on the Usage of Chitosan for Photonics and Nanomaterials Research

“…Based on these requirements, the following is hypothesized: Highly desirable hybrid nanostructure [ 8 , 49 ] would be formed by stabilizing imaging agents in aqueous solution encapsulated with polymeric materials that can form nanoparticles, and possess reactive functional groups for further bio-conjugation. Therefore, CSNPs containing a luminescent agent (referred to as luminescent CS nanoparticles) are very attractive candidates, especially for in vitro drug delivery, cell imaging, biodistribution, diagnostic imaging of cancer cells, labeling of stem cells, imaging of pathogenic cells, temperature sensors, killing cancer cells, and other biomedical purposes [ 8 , 45 , 48 , 50 , 51 ]. For all such applications, CSNPs are either loaded or cross-linked with a luminescent reagent that exhibits photoluminescence on excitation with UV or visible wavelength light.…”

“…The CaF 2 :Eu nanoparticles are first stabilized within CS polymer via its capping ability, followed by utilizing the amine groups on CS for crosslinking with biomolecules and proteins like Bovine Serum Albumin (BSA) [ 44 ]. In some cases, the existing nanoparticles or nanoclusters are self-assembled using modified CS systems [ 51 ] or crosslinked with CS using selective crosslinking agents. Other works include studies detailing the synthesis of fluorescent CS nanoparticles using FITC-labeled CS.…”

“…Metal nanoclusters, usually ranging in size from several atoms to tens of atoms, have received enormous attention in the last decade [ 51 ]. The metal nanoclusters show special properties such as discrete electronic states, size-dependent fluorescence, and intrinsic magnetism [ 51 ].…”

“…Metal nanoclusters, usually ranging in size from several atoms to tens of atoms, have received enormous attention in the last decade [ 51 ]. The metal nanoclusters show special properties such as discrete electronic states, size-dependent fluorescence, and intrinsic magnetism [ 51 ]. Gold nanoclusters specifically exhibit excellent properties quite different from QDs and traditional organic dyes, such as low toxicity, good chemical and photo-physical stability, easy synthesis, and tunable fluorescence [ 51 ].…”