Controlling the Cytotoxicity of CdSe Magic-Sized Quantum Dots as a Function of Surface Defect Density Anielle Christine Almeida Silva,* ,† Marcelo Jose ́ Barbosa Silva, ‡ Felipe Andre ́ s Cordero da Luz, ‡ Danielle Pereira Silva, ‡ Samantha Luara Vieira de Deus, †,‡ and Noelio Oliveira Dantas* ,† † Laborató rio de Novos Materiais Isolantes e Semicondutores (LNMIS), Instituto de Física, Universidade Federal de Uberlâ ndia, Uberlâ ndia, Brazil ‡ Laborató rio de Osteoimunologia e Imunologia dos Tumores, Instituto de Ciê ncias Biome ́ dicas (ICBIM) - Universidade Federal de Uberlâ ndia, Uberlâ ndia, MG Brazil * S Supporting Information ABSTRACT: Quantum dots are potentially very useful as fluorescent probes in biological systems. However, they are inherently cytotoxic because of their constituents. We controlled the cytotoxicity of CdSe magic-sized quantum dots (MSQDs) as a function of surface defect density by altering selenium (Se) concentration during synthesis. Higher Se concentrations reduced the cytotoxicity of the CdSe MSQDs and diminished mRNA expression of methallothio- nein because of the low cadmium ions (Cd 2+ ) concentration adsorbed on the surface of the MSQDs. These results agree with luminescence spectra, which show that higher Se concentrations decrease the density of surface defects. Therefore, our results describe for the first time a simple way of controlling the cytotoxicity of CdSe MSQDs and making them safer to use as fluorescence probes in biological systems. KEYWORDS: Cytotoxicity, CdSe MSQDs, methallothionein, HeLa cells, surface defect levels Q uantum dots (QDs) are widely used in applications such as drug delivery, 1 fluorescent probes, 2,3 cancer diagnosis and therapy, 4 and biosensors. 5 In biological applications, QDs have several advantages over more traditional fluorescent proteins and organic fluorophores because of their high quantum efficiency and photostability. 6 However, QDs are inherently toxic because of their small size, which allows them to interfere in various cell signaling pathways. 7-9 Several studies on diverse types of cadmium-containing QDs have shown different cell responses caused by other coating properties and compounds in their cores or shells. Various noxious effects caused by QDs in vitro have been reported. Cell death (necrosis and apoptosis) induced by oxidative-stress re- sponse 10,11 and many associated cellular mechanisms have been observed. These include elevated cytochrome c 11,12 and calcium 13 in the cytoplasm and upregulation of Fas, a death receptor on the surface of the cell that leads to apoptosis. 14 Furthermore, the oxidative-stress response of the cell causes upregulation of the genes involved in metal ion buffering, such as metallothionein 1 and 2. 15 Cells treated with QDs also show cell membrane damage, changes to mitochondrial properties, nuclei shrinkage, metabolic reduction, chromatin condensa- tion, 14 cell-cycle alterations (premature cell division), 12 abnormal spindles, and chromosomes in mitotic cells. 15 This oxidative-stress response is caused by cadmium ions (Cd 2+ ) adsorbed on the surface of the QDs that interact with oxygen molecules in the cells. 16 Nevertheless, a certain level of cadmium ions is well-tolerated by the cells. Additionally, some Received: July 22, 2014 Revised: August 25, 2014 Published: August 27, 2014 Letter pubs.acs.org/NanoLett © 2014 American Chemical Society 5452 dx.doi.org/10.1021/nl5028028 | Nano Lett. 2014, 14, 5452-5457