Colloids and Surfaces B: Biointerfaces 111 (2013) 142–149 Contents lists available at SciVerse ScienceDirect Colloids and Surfaces B: Biointerfaces jou rn al hom epage: www.elsevier.com/locate/colsurfb Cytocompatibility evaluation of glycol-chitosan coated boron nitride nanotubes in human endothelial cells Serena Del Turco a,∗,1 , Gianni Ciofani b,1 , Valentina Cappello c , Mauro Gemmi c , Tiziana Cervelli a , Chiara Saponaro a , Simone Nitti d , Barbara Mazzolai b , Giuseppina Basta a , Virgilio Mattoli b a Institute of Clinical Physiology, CNR, San Cataldo Research Area, via Moruzzi, 1, 56124 Pisa, Italy b Center for Micro-BioRobotics@SSSA, Fondazione Istituto Italiano di Tecnologia, Viale Rinaldo piaggio 34, 56025 Pontedera (Pisa), Italy c Center for Nanotechnology Innovation@NEST, Fondazione Istituto Italiano di Tecnologia, Piazza S. Silvestro 12, 56127 Pisa, Italy d Department of Nanochemistry, Fondazione Istituto Italiano di Tecnologia, via Morego 30, 16163 Genova, Italy a r t i c l e i n f o Article history: Received 10 December 2012 Received in revised form 16 April 2013 Accepted 18 May 2013 Available online 25 May 2013 Keywords: Endothelial cells Boron nitride nanotubes In vitro testing Cell activation a b s t r a c t Boron nitride nanotubes (BNNTs) are intriguing nanomaterials with a wide range of potential biomedi- cal applications. The assessment of BNNT interactions with biological systems, at both the cellular and subcellular levels, is an essential starting point for determining their bio-safety. We explore the effects of increasing concentrations of GC-BNNTs (0–100 g/mL) on human vein endothelial cells (HUVECs), testing cell toxicity, proliferation, cytoskeleton integrity, cell activation and DNA damage. No significant changes were observed in cell viability, cytoskeleton integrity or DNA damage. Only a modest reduction in cell viability, tested by trypan blue assay, and the increased expression of vascu- lar adhesion molecule-1, a marker of cell activation, were detected at the highest concentration used (100 g/mL). Taken together, these findings indicate that GC-BNNTs do not affect endothelial cell biology, and are a promising first step in further investigation of their application potential in vascular targeting, imaging, and drug delivery. © 2013 Elsevier B.V. All rights reserved. 1. Introduction The rapid progress of nanoscience and the application of nano- technology have opened new vistas in diagnosis, treatment, and prevention of cardiovascular disease. In cardiovascular disease, biomedical applications of nanotechnology have the potential to develop new diagnostic imaging agents, targeted therapeutics and devices in one nanostructure with unique physical and chemi- cal properties [1]. The benefits and side effects of these technical advances must be evaluated carefully [2]. An accurate assessment of nanomaterial bio-safety in vitro and in animal models is imper- ative, and their ultimate role must be established in clinical trials to ensure public safety and approval. Boron nitride nanotubes (BNNTs) are an attractive material structurally analogous to a common carbon nanotube (CNT): alternating B and N atoms entirely substitute for C atoms in a graphitic-like sheet with almost no changes in atomic spacing [3]. ∗ Corresponding author. Tel.: +39 050 315 2661; fax: +39 050 315 2166. E-mail address: serena@ifc.cnr.it (S. Del Turco). 1 These authors contributed equally to this work. In spite of this structural similarity with CNTs, BNNTs have superior mechanical, chemical, and electrical properties [4]. While a broad range of potential applications of CNTs has been proposed in the last few years as nanovectors for drug, protein and gene delivery, DNA chips and biosensors [5], biomedical applications of BNNTs are as yet largely unexplored. Many contrasting results are emerg- ing regarding the cytocompatibility of nanomaterials with living systems, and thus the biological testing of interactions between BNNTs and living systems is a priority, before their exploitation in the biomedical field. In vitro studies have assessed BNNT–cell interactions in differ- ent cell lines, such as human neuroblastoma [6], muscle cells [7], embryonic kidney [8], murine alveolar macrophage and embryonic fibroblast cells [9], also showing contradictory results. Since the effects of nanomaterials vary depending on the cell type, localiza- tion and physiological role, it is crucial to assess them in various cell models. The study of the interaction between endothelial cells and nanomaterials is interesting for two main reasons. First, endothe- lium is the first barrier of the vessel wall that nanomaterials meet after their administration, before reaching specific tissue targets or being eliminated [10]. Secondly, the endothelium plays a key role in cardiovascular physiopathology. In fact, healthy endothelium plays 0927-7765/$ – see front matter © 2013 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.colsurfb.2013.05.031