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

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.