Nanomedicine and epigenome. Possible health risks

Abstract

a b s t r a c tNanomedicine is an emerging field that combines knowledge of nanotechnology and material science with pharmaceutical and biomedical sciences, aiming to develop nanodrugs with increased efficacy and safety. Compared to conventional therapeutics, nanodrugs manifest higher stability and circulation time, reduced toxicity and improved targeted delivery. Despite the obvious benefit, the accumulation of imaging agents and nanocarriers in the body following their therapeutic or diagnostic application generates concerns about their safety for human health. Numerous toxicology studies have demonstrated that exposure to nanomaterials (NMs) might pose serious risks to humans. Epigenetic modifications, representing a non-genotoxic mechanism of toxicant-induced health effects, are becoming recognized as playing a potential causative role in the aetiology of many diseases including cancer. This review i) provides an overview of recent advances in medical applications of NMs and ii) summarizes current evidence on their possible epigenetic toxicity. To discern potential health risks of NMs, since current data are mostly based upon in vitro and animal models, a better understanding of functional relationships between NM exposure, epigenetic deregulation and phenotype is required.

Nanotoxicity: a challenge for future medicine

“…Nanotoxicology studies such as in vivo-like on 3D human organs, cells also advanced genetic studies are beginning to replace conventional in vitro analytical methods [151,152]. In vitro testing methods might require assessment of multiple challenging steps such as physicochemical properties of nanomaterials, the environment-target cell, cellular uptake and epigenetic interaction [153]. Omic approaches; next generation sequencing, transcriptomics and proteomics, have provided considerably more information regarding the toxicity of the complex cellular processes triggered by interaction of nanomaterials with the microenvironment [154,155].…”

Immunotoxicity, genotoxicity and epigenetic toxicity of nanomaterials: New strategies for toxicity testing?

“…The recent review of Clark and colleagues focuses on single cell epigenomic methods and their application for understanding gene regulation (Clark et al, 2016). The emerging evidence shows that NM-induced changes in gene expression do not occur at predictable locations (reviewed in Smolkova et al, 2015;Smolkova et al, 2017)). This is the reason why WGA are, despite their costs, the most promising approach to test epigenetic toxicity of NMs.…”

“…It is especially important, as epigenetic toxicity has been induced by NMs and occurred at sub-cytotoxic and sub-genotoxic concentrations (Ghosh et al, 2017). OECD-recommended methods should be preferred where possible, but new tests such as for epigenetic toxicity endpoints (Smolkova et al, 2015(Smolkova et al, , 2017 need to be developed as OECD methods for these endpoints do not exist. Possible interference with the standard assays should be tested .…”

“…The demand to move from animal models to novel technologies arises from various concerns, including the need to evaluate large numbers of new NM products, the limited predictivity of traditional tests for human health effects, duration and costs of current approaches, and animal welfare considerations. Existing in vitro test methods need further modifications taking into considerations challenges related to NM physicochemical properties and their interaction with surrounding and target environments, cellular uptake and novel endpoints, particularly epigenetics (Stefanska et al, 2012;Smolkova et al, 2017).…”

“…Recent research has raised concern about possible epigenetic toxicity and health effects induced by NMs (Jennifer and Maciej, 2013;Shyamasundar et al, 2015;Smolkova et al, 2015Smolkova et al, , 2017. Epigenetic toxicology is a novel area of research, that examines epigenetic alterations induced by environmental exposures and their implications for public health.…”