Research Article Effects of Two Fullerene Derivatives on Monocytes and Macrophages Sabrina Pacor, 1 Alberto Grillo, 1 Luka YorZeviT, 2 Sonia Zorzet, 1 Marianna Lucafò, 1 Tatiana Da Ros, 2 Maurizio Prato, 2 and Gianni Sava 1,3 1 Department of Life Sciences, University of Trieste, Via L. Giorgieri 5, 34127 Trieste, Italy 2 Department of Chemical and Pharmaceutical Sciences, University of Trieste, Via L. Giorgieri 5, 34127 Trieste, Italy 3 Callerio Foundation, Institutes of Biological Research, Via A. Fleming 22-31, 34127 Trieste, Italy Correspondence should be addressed to Sabrina Pacor; pacorsab@units.it Received 27 June 2014; Revised 10 September 2014; Accepted 24 September 2014 Academic Editor: Amitava Mukherjee Copyright © 2015 Sabrina Pacor et al. his is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Two fullerene derivatives (fullerenes 1 and 2), bearing a hydrophilic chain on the pyrrolidinic nitrogen, were developed with the aim to deliver anticancer agents to solid tumors. hese two compounds showed a signiicantly diferent behaviour on human neoplastic cell lines in vitro in respect to healthy leukocytes. In particular, the pyrrolidinium ring on the fullerene carbon cage brings to a more active compound. In the present work, we describe the efects of these fullerenes on primary cultures of human monocytes and macrophages, two kinds of immune cells representing the irst line of defence in the immune response to foreign materials. hese compounds are not recognized by circulating monocytes while they get into macrophages. he evaluation of the pronecrotic or proapoptotic efects, analysed by means of analysis of the purinergic receptor P2X7 activation and of ROS scavenging activity, has allowed us to show that fullerene 2, but not its analogue fullerene 1, displays toxicity, even though at concentrations higher than those shown to be active on neoplastic cells. 1. Introduction Application of nanomaterials is increasing in the ield of medicine with the aim to overcome the limitations of or to provide new tools and solutions to the existing approaches to human diseases [1, 2]. Among these nanoscale chemical structures, fullerenes represent an important source of the so- called biocompatible molecules because of their capacity to be in contact with cells and biological tissues without altering their behaviour [3]. Some of these substances were shown to be capable to cross cells without afecting their viability [4, 5]; others were demonstrated to be suitable as substrates for the growth of cells and tissues of importance for regenerative medicine and cell therapies [6]. hey are also supposed to be good drug carriers in that they might use the enhanced permeability retention for selective accumulation of cytotoxic agents into solid tumour masses [7, 8]. In this context, two fullerene derivatives (hereater iden- tiied as fullerene 1 and fullerene 2, Figure 1), bearing a hydrophilic chain on the pyrrolidinic nitrogen, were devel- oped with the aim to deliver anticancer agents to solid tumours [9]. hese two compounds showed a signiicantly diferent behaviour on cell cultures in vitro, as the charged compound 2 is being signiicantly more cytotoxic than fullerene 1. A whole-transcriptome RNA-seq analysis, assess- ing their efects on gene expression in the human MCF7 cell line [10], highlighted the questions about the safety of fullerenes in biological systems. In fact, also those com- pounds (e.g., fullerene 1) which appear to be well tolerated, according to conventional functional studies, can cause important changes at the transcriptomic level, suggesting potential implications for the toxicity of these compounds. he efects of nanomaterials for immune cells have even major health, hazard identiication and risk assessment implications. his is particularly important when proposing their possible use as drug delivery devices in tumor-bearing patients for whom the maintenance of an appropriate func- tionality of the immune system is of crucial importance for Hindawi Publishing Corporation BioMed Research International Volume 2015, Article ID 915130, 13 pages http://dx.doi.org/10.1155/2015/915130