The cardiovascular effects of engineered nanoparticles
There has been an exponential increase in the production and development of manufactured nanomaterials (MNMs) for wide-ranging applications. However, there is potential for MNMs to harm the cardiovascular system (as environmental nanoparticles do). This possibility remains largely unexplored.
There has been an exponential increase in the production of manufactured nanomaterials (MNMs) for a wide variety of applications, including engineering, electronic circuitry, food preservatives, clothes, water purification, batteries, paints, sun-creams and medical therapeutics. However, research into the potential for MNM exposure to induce toxicity is lagging behind the interest in their development. This is especially concerning given that these materials share many physicochemical properties with combustion-derived nanoparticles in air pollution, which our group has previously shown to induce multiple detrimental effects on the cardiovascular system. The potential for MNMs to harm the cardiovascular system is very poorly understood.
Our group has a series of projects that will investigate the cardiovascular effects of MNMs.
NanoMILE: “Engineered nanomaterials mechanisms of interaction with living systems and the environment: a universal framework for safe nanotechnology”
NanoMILE is a European Union funded large collaborative FP7 programme of 28 partner institutions across Europe (Lead: University of Birmingham). The programme will synthesise, characterize and comprehensively test the biological toxicity of MNMs in the environment and mammalian models. Multiple organ systems will be considered (e.g. pulmonary, reticuloendothelial system, neurobehaviour). The University of Edinburgh partners (PI: Miller) will explore the cardiovascular effects of MNMs using a series of complementary in vitro, cellular, in vivo and clinical models. Currently we are studying redox-modified cerium oxide and cobalt oxide MNMs, as well as dextran-coated ultra-small paramagnetic iron oxide nanoparticles (U-SPIONs).
Lipid mediators to predict MNM toxicity
At present the ‘signal’ that links the pulmonary to the cardiovascular effects of inhaled MNMs has yet to be established. We hypothesise that inhaled nanoparticles trigger different cells in the lung to release lipid mediators called eicosanoids, which pass into the circulation and modify cardiovascular function, as well as induce inflammation and oxidative stress. A BHF Special Project Grant (PI: Miller)-funded collaboration with the University of the Highlands and Islands will investigate a panel of carbonaceous MNMs including, nanosized carbon black, environmental carbon-based nanoparticles, carbon nanotubes and different forms of graphene.
Nanoparticles themselves may be small enough to pass (“translocate”) from the lung to the circulation and directly interact with the vascular system. A small proportion of the complexities of nanoparticle clearance and translocation from the lung are highlighted in Figure 2 (Stone et al., 2017; EHP 125:106002. Figure by Miller, based on a COST MODENA-funded workshop). In a Colt Foundation-funded Project Grant (PI: Duffin, Centre
for Inflammation Research) we look at the ability of different sizes of gold nanoparticles, a commonly used MNM, to access the circulation. We have shown, in animal models and human volunteers, that inhaled nanoparticles not only reach the circulation, but also accumulate at sites of vascular inflammation where they are most likely promote the development of disease (Miller et al., 2017; ACS Nano 11:4542-52).
Principal Investigator, Co-Investigators, Other researchers
Mark Miller, Lorraine Bruce, David Newby, Nicholas Mills, Anoop Shah, Simon Wilson, Jack Andrews, Paddy Hadoke, Ian Smith (CRH), Rodger Duffin (CIR), Jennifer Raftis (CIR), Ian Megson (UHI), Phil Whitfield (UHI), Eva Valsami-Jones (UoB), Susan Dekkers (RIVM), Flemming Cassee (RIVM), Wim de Jong (RIVM)