Rom J Morphol Embryol 2014, 55(2 Suppl):545–551 ISSN (print) 1220–0522 ISSN (on-line) 2066–8279 ORIGINAL PAPER Silica network improve the effect of fludarabine and paclitaxel on HCT8 cell line GEORGETA VOICU 1) , ADRIAN GABRIEL ANGHEL 2) , MIHAELA BADEA 2) , EMANOIL BORDEI 2) , GEORGIANA CRANTEA 2) , RALUCA IONELA GAVRILĂ 2) , ALEXANDRU GRECU 2) , DENISA ANA-MARIA JERCAN 2) , BOGDAN CRISTIAN NICOLAE 2) , GRETA CRISTINA VOCHIŢOAIA 2) , KUETE TCHINDA 2) , ALINA MARIA HOLBAN 1) , CORALIA BLEOTU 3) , ALEXANDRU MIHAI GRUMEZESCU 1) 1) Department of Science and Engineering of Oxide Materials and Nanomaterials, Faculty of Applied Chemistry and Materials Science, Politehnica University of Bucharest, Romania 2) Department of Biomaterials and Medical Devices, Faculty of Medical Engineering, Politehnica University of Bucharest, Romania 3) “Ştefan S. Nicolau” Institute of Virology, Bucharest, Romania Abstract This paper reports the potential of silica network to sensitize tumor cells and stimulate antitumor toxicity of fludarabine (FLU) and paclitaxel (PAC) against HCT8 cells. SiO2, SiO2/FLU and SiO2/PAC nanostructured materials were characterized by X-Ray Diffraction, Scanning Electron Microscopy, InfraRed Microscopy and in vitro biological assays. When using SiO2/PAC, it can be observed that the cytostatic effect of PAC is boosted only at high concentrations of this material. On the other hand, in the case of SiO2/FLU, data showed an enhancement in the cytostatic activity of FLU by up to 25%, also when using this nanomaterial in low doses. These data represent preliminary study on the impact on silica nano-networks in targeted delivery and controlled release of antitumor drugs and they may be efficiently used for future biomedical applications in cancer therapy. Keywords: fludarabine, paclitaxel, antitumoral, silica network, cell viability. Introduction Applications of nanotechnology in the treatment of cancer have attracted the attention of researchers due to the great potential of nanomaterials to be used for two or more different functions [1–10]. Multifunctional nano- materials have been designed for various applications such as drug delivery, imaging or diagnostic sensors [11– 13]. Inorganic or organic nanomaterials were involved in the development of various applications in cancer therapy [14–18]. Silica nanomaterials were successfully used in the cancer therapy due to their easy route of synthesis, easy functionalization and adjustable pore volume [19–23]. Silica networks are usually non-toxic and frequently used in biomedical applications [24, 25]. Two types of silica network were designed during recent years: core/shell nanoparticles and mesoporous nano- particles [26, 27]. Core/shell nanoparticles are consisting of a metal oxide as a core and silica as a shell, usually prepared from tetraethyl orthosilicate or sodium meta- silicate [28, 29]. Mesoporous silica nanoparticles are usually prepared by templating using various surfactants [30, 31]. In a recent study, γ-amino-butyric acid was used as templating agent for the preparation of a newly silica network able to deliver and improve the effect of therapeutic agents [32]. The dimension of particle was estimated at 10 nm from TEM analysis, while BET analysis reveal the average pores diameters of 4.6 nm, as revealed by this study [32]. Different formulations based on silica networks and antitumor agents can be found in recent literature, but no data explaining the interaction of silica networks with antitumoral agents in the light of any improvements of the antitumor effects of the active drug, was reported. Here, we reveal the ability of silica network to deliver and improve the antitumor effect of fludarabine (FLU) and paclitaxel (PAC) against cultured HCT8 tumor cells, which may be used for future research with applications in cancer therapy. Materials and Methods Materials Sodium metasilicate, sulfuric acid (ACS reagent 95– 98%) and ε-amino-caproic acid were purchased from Sigma-Aldrich, and were used without any further purification. Preparation of silica network Silica network was prepared from sodium metasilicate by treating with 5% sulfuric acid. In a 500 mL beaker was added under vigorous stirring, 100 mL water, 20 mL Na 2 SiO 3 ×H 2 O and 1 g of ε-amino-caproic acid. After 10 minutes of vigorous stirring, sulfuric acid solution was added drop by drop, under permanent stirring until the pH was up to 7, leading the formation of transparent hydrogel. The prepared hydrogel was filtered, repeatedly washed with deionized water, and subsequently dried at room temperature. In the next step, the dried powder was calcinated at 650 0 C for 24 hours in order to remove the ε-amino-caproic acid. R J M E Romanian Journal of Morphology & Embryology http://www.rjme.ro/