Cytotoxicity of nucleus-targeting fluorescent gold nanoclusters

Abstract

Gold nanoclusters (AuNCs) with ultra small sizes and unique fluorescence properties have shown promising potential for imaging the nuclei of living cells. However, little is known regarding the potential cytotoxicity of AuNCs after they enter the cell nucleus. The aim of this study is to investigate whether and how nucleus-targeting AuNCs affect the normal functioning of cells. Highly stable, water-soluble and bright fluorescent Au25NCs (the core of each nanocluster is composed of 25 gold atoms) were synthesized. Specific targeting of Au25NCs to the cell nucleus was achieved by conjugating the TAT peptide to the Au25NCs. Cell viability, cell morphology, cell apoptosis/necrosis, reactive oxygen species (ROS) level and mitochondrial membrane potential examinations were performed on different cell lines exposed to the nucleus-targeting Au25NCs. We found that the nucleus-targeting Au25NCs caused cell apoptosis in a dose-dependent manner. A possible mechanism for the cytotoxicity of the nucleus-targeting Au25NCs was proposed as follows: the nucleus-targeting Au25NCs induce the production of ROS, resulting in the oxidative degradation of mitochondrial components, in turn leading to apoptosis via a mitochondrial damage pathway. This work facilitates a better understanding of the toxicity of AuNCs, especially nucleus-targeting AuNCs.

Photoluminescent Gold Nanoclusters in Cancer Cells: Cellular Uptake, Toxicity, and Generation of Reactive Oxygen Species

“…Therefore, the small size of Au-MES NCs allows them to pass through the cell membrane and even through nuclear membrane diffusely. Large nanoparticles of the sizes up to 30 nm in diameter including BSA-Au NCs can also target nuclei, yet, in order to pass the nuclear envelope their surface has to be modified with nuclear localization signals [61,62]. Nanoparticles without proper nuclear localization signal are packed in endosomes upon entering the cells and cannot escape endocytic vesicles [61], therefore, BSA-Au NCs as well as BSA were observed accumulated in vesicles at the perinuclear region, but not inside the cell nucleus.…”

Carbon nanotubes allow capture of krypton, barium and lead for multichannel biological X-ray fluorescence imaging

“…The often diffuse biodistribution of naturally occurring elements in these prior studies means that features, such as organelles and membranes can be poorly defined and ambiguity arises/would arise from use of these elements as labels, thereby hindering interpretation of associated maps. While some elegant studies have made use of xenobiotic elements as contrast agents4849505152, there has been no general method until now that would permit wide-ranging variation of both targeting ligand and XRF tag element.…”

Protein-gold clusters-capped mesoporous silica nanoparticles for high drug loading, autonomous gemcitabine/doxorubicin co-delivery, and in-vivo tumor imaging

“…[63] When compared to gold nanoparticles (AuNPs), [64] AuNCs-proteins have proved to be safer and more reliable imaging probes. [65] Interestingly, few reports have recently described the unique nuclei staining properties of AuNCs, [66,67] which could allow the study of important biological processes such as mitosis. [67] This nuclei targeting is also the origin of several drug delivery studies, [68][69][70][71] such as DOX delivery via AuNC@BSA combined with two-photon imaging.…”

“…[65] Interestingly, few reports have recently described the unique nuclei staining properties of AuNCs, [66,67] which could allow the study of important biological processes such as mitosis. [67] This nuclei targeting is also the origin of several drug delivery studies, [68][69][70][71] such as DOX delivery via AuNC@BSA combined with two-photon imaging. [72] AuNCs were also covalently grafted on non-porous silica NPs for cytosol imaging and reactive oxygen species detection via the quenching of the gold fluorescence, [73] however, AuNCs were not combined with MSN.…”