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Cytotoxicity of BSA-Stabilized Gold Nanoclusters: In Vitro and In Vivo Study

Significance Statement

Biomolecules-stabilized Gold Nanoclusters: Are They Really Safe in Biomedicine?

Gold nanoparticles (Au NPs) have shown promising potentials in bio-imaging, diagnostics, drug delivery, and photothermal cancer therapy. Interestingly, decreasing size of Au NPs (e.g., Au nanoclusters (NCs)) to less than 1 nm (a few atoms) allows the NPs strongly express fluorescence. Compared to CdSe quantum dots, biomolecules-coated Au NCs demonstrate more photo-stability, lower toxicity, and good biocompatibility due to their lower metallic content, potentially useful in bio-imaging, bio-sensing and bio-labeling. Moreover, Au NCs exhibit good water solubility, abundant surface functionalities, increased circulation time and preferential accumulation in tumor sites, leading to great promise in biomedicine applications. Before clinical application, it is highly desirable to access and evaluate comprehensively potential toxicity of gold nanoclusters . Usually, gold nanoclusters , especially biomolecules-coated gold nanoclusters , were believed to be biocompatible and no toxicity was observed in previous reports. Yet, most of these studies were performed on few cell lines, short incubation period and narrow Au NCs concentration range. Thus, safety of Gold Nanoclusters was not strongly evidenced, and there has been no systemic investigation on cytotoxicity of Au NCs. Recently, Juan Tao’s and Jintao Zhu’s group in Huazhong University of Science and Technology systemically investigated biological effect of bovine serum albumin (BSA)-coated gold nanoclusters in vitro and in vivo. Biocompatible BSA-coated Au NCs was selected as a model system while three tumor cell lines and two types of normal cells were chosen to investigate cellular uptake, viability, apoptosis, and intracellular reactive oxygen species (ROS) generation for long-term exposure with a wide range of concentrations. Gold nanoclusters could enter cells quickly and exhibited varied levels of cytotoxicity in certain concentration range of Au NCs on different cells. Free BSA molecules in the Gold nanoclusters solutions could partly counteract the toxicity effect posed by gold nanoclusters , which might explain the obvious toxicity of gold nanoclusters within a certain concentration range (5 and 20 nM). Intracellular ROS generation by BSA-Au NCs was one of the important mechanisms of toxicity which could be alleviated by the ROS scavenger. Moreover, toxicity of Au NCs was confirmed in mouse models with subcutaneous HepG-2 liver tumor and Au NCs could markedly inhibit the tumor growth. This research was published in Small (2015, DOI: 10.1002/smll.201403481). This study implied that care should be taken on the biocompatibility and potential toxicity of new nanomaterials before translation to clinic applications. Moreover, this study is useful for designing Au NCs with specific stabilizers for biomedical applications, including bio-imaging, drug delivery and targeting, cancer therapy by selecting varied dose and incubation time.

Cytotoxicity of BSA-Stabilized Gold Nanoclusters In Vitro and In Vivo Study. Global Medical Discovery






Usually, biomolecules-coated Au nanoparticles are believed to be biocompatible. This study showed that BSA-stabilized Au NCs could induce decline of cell viabilities on different cells and inhibit tumor growth to varied degree in a dose- and time-dependent manner, providing a new opportunity for design of anti-cancer drugs.

Journal Reference

Dong L, Li M, Zhang S, Li J, Shen G, Tu Y, Zhu J, Tao J. Small. 2015 Jan 28.

Department of Dermatology, Affiliated Union Hospital, Tongji Medical College, Huazhong University of Science and Technology (HUST), Wuhan, 430022, China.


Gold nanoclusters (Au NCs) are one of the most promising fluorescent nanomaterials for bioimaging, targeting, and cancer therapy due to their tunable optical properties, yet their biocompatibility still remains unclear. Herein, the cytotoxicity of bovine serum albumin (BSA)-stabilized gold nanoclusters is studied by using three tumor cell lines and two normal cell lines. The results indicate that gold nanoclusters  induce the decline of cell viabilities of different cell lines to varying degrees in a dose- and time-dependent manner, and umbilical vein endothelial cells which had a higher intake of gold nanoclusters  than melanoma cells show more toxicity. Addition of free BSA to BSA-Au NCs solutions can relieve the cytotoxicity, implying that BSA can prevent cell damage. Moreover, gold nanoclusters  increase intracellular reactive oxygen species (ROS) production, further causing cell apoptosis. Furthermore, N-acetylcysteine, a ROS scavenger, partially reverses gold nanoclusters -induced cell apoptosis and cytotoxicity, indicating that ROS might be one of the primary reasons for the toxicity of BSA-gold nanoclusters . Surprisingly, gold nanoclusters  with concentrations of 5 and 20 nM significantly inhibit tumor growth in the xenograft mice model of human liver cancer, which might provide a new avenue for the design of anti-cancer drug delivery vehicles.

© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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