Cytotoxicity of mesoporous silica nanomaterials Anthony J. Di Pasqua a , Krishna K. Sharma a , Yan-Li Shi a , Bonnie B. Toms b , Wayne Ouellette a , James C. Dabrowiak a, * , Tewodros Asefa a, * a Department of Chemistry, Syracuse University, 111 College Place, CST, Rm 1-014, Syracuse, NY 13244-4100, United States b Department of Pediatrics, Upstate Medical University, State University of New York, 750 East Adams Street, Syracuse, NY 13210, United States Received 19 September 2007; received in revised form 20 December 2007; accepted 24 December 2007 Available online 9 January 2008 Abstract We here measure the toxicity of MCM-41, a mesoporous silica nanomaterial, two of its functionalized analogs, AP-T, which has grafted aminopropyl groups and MP-T, which has grafted mercaptopropyl groups, and spherical silica nanoparticles (SiO 2 ), toward human neuroblastoma (SK–N–SH) cells. Since the particles studied are not soluble in aqueous media, the metric used to report the cyto- toxicity of these materials is a new quantity, Q 50 , which is the number of particles required to inhibit normal cell growth by 50%. Deter- mining the number of particles per gram of material applied to the cells required both the calculated and experimentally determined surface areas of these nanomaterials. This study shows that Q 50 increases in the order, MCM-41 < MP-T < AP-T  SiO 2 , showing that on a per particle basis, MCM-41 is the most cytotoxic material studied. For the three mesoporous silica materials in this study, cytotox- icity appears related to the adsorptive surface area of the particle, although the nature of the functional group cannot be ruled out. Silica nanospheres have the lowest surface area of the particles studied but since they exhibit a Q 50 value similar to that of AP-T, shape may also be important in the cytotoxicity of these materials. Ó 2008 Elsevier Inc. All rights reserved. Keywords: Cells; Cytotoxicity; Nanomaterials; Mesoporous silica 1. Introduction The use of nanomaterials as high capacity drug delivery agents is being actively investigated [1–10]. One of the most important members of this class of materials is mesoporous silica, which is a nanometer sized ridged assembly of silica channels (pores) capable of adsorbing small molecules [11,12]. Since the surface of mesoporous silica can be func- tionalized with different organic groups through grafting procedures, this material has considerable potential for selective adsorption and release of drugs in new types of therapeutic strategies [13–16]. Devoiselle and coworkers recently showed that meso- porous silica MCM-41 has the ability to adsorb and release ibuprofen [13]. Deng and coworkers further demonstrated that rate of ibuprofen release from MCM-41 can be reduced by grafting trimethylsilyl groups onto the ibupro- fen-impregnated material [14]. Zhu and coworkers showed that MCM-41 has the capacity to adsorb and release aspi- rin, and that release of this drug is affected by the number of aminopropyl groups present on the pore wall of the material [16]. More recently, mesoporous silica nanoparti- cles were used to deliver a hydrophobic anticancer agent to human cancer cells [17]. It has already been shown that mesoporous silica nanoparticles are taken into the cell via an endocytotic mechanism [7]. If such materials are to be used in vivo, i.e. as vehicles for drug delivery, a measure of each material’s cytotoxicity must be clearly defined. However, the extent to which non- and functionalized mesoporous silica, and indeed many other types of nanomaterials currently being studied, are toxic to mammalian cells has not yet been fully explored [18–23]. Usually, the cytotoxicity of a drug, toxin, 0162-0134/$ - see front matter Ó 2008 Elsevier Inc. All rights reserved. doi:10.1016/j.jinorgbio.2007.12.028 * Corresponding authors. Tel.: +1 315 443 4601; fax: +1 315 443 4070 (J.C. Dabrowiak), tel.: +1 315 443 3360 (T. Asefa). E-mail addresses: jcdabrow@syr.edu (J.C. Dabrowiak), tasefa@syr. edu (T. Asefa). www.elsevier.com/locate/jinorgbio Available online at www.sciencedirect.com Journal of Inorganic Biochemistry 102 (2008) 1416–1423 JOURNAL OF Inorganic Biochemistry