An overview on dispersion procedures and testing methods for the ecotoxicity testing of nanomaterials in the marine environment.

Considerable efforts have been devoted to develop or adapt existing guidelines and protocols, to obtain robust and reproducible results from (eco)toxicological assays on engineered nanomaterials (NMs). However, while many studies investigated adverse effects of NMs on freshwater species, less attention was posed to the marine environment, a major sink for these contaminants. This review discusses the procedures used to assess the ecotoxicity of NMs in the marine environment, focusing on the use of protocols and methods for preparing NMs dispersions and on the NMs physicochemical characterization in exposure media. To this purpose, a critical analysis of the literature since 2010 was carried out, based on the publication of the first NMs dispersion protocols. Among the 89 selected studies, only <5 % followed a standardized dispersion protocol combined with NMs characterization in ecotoxicological media, while more than half used a non-standardized dispersion method but performed NMs characterization. In the remaining studies, only partial or no information on dispersion procedures or on physicochemical characterization was provided. This literature review also highlighted that metal oxides NMs were the most studied (42 %), but with an increasing interest in last years towards nanoplastics (14 %) and multicomponent nanomaterials (MCNMs, 7 %), in line with the growing attention on these emerging contaminants. For all these NMs, primary producers as algae and bacteria were the most studied groups of marine species, in addition to mollusca, while organisms at higher trophic levels were less represented, likely due to challenges in evaluating adverse effects on more complex organisms. Thus, despite the wide use of NMs in different applications, standard dispersion protocols are not often used for ecotoxicity testing with marine species. However, the efforts to characterize NMs in ecotoxicological media recognize the importance of following conditions that are as standardized as possible to support the ecological hazard assessment of NMs.

Using Stock-Flow Diagrams to Visualize Theranostic Approaches to Solid Tumors in Personalized Nanomedicine.

Personalized nanomedicine has rapidly evolved over the past decade to tailor the diagnosis and treatment of several diseases to the individual characteristics of each patient. In oncology, iron oxide nano-biomaterials (NBMs) have become a promising biomedical product in targeted drug delivery as well as in magnetic resonance imaging (MRI) as a contrast agent and magnetic hyperthermia. The combination of diagnosis and therapy in a single nano-enabled product (so-called theranostic agent) in the personalized nanomedicine has been investigated so far mostly in terms of local events, causes-effects, and mutual relationships. However, this approach could fail in capturing the overall complexity of a system, whereas systemic approaches can be used to study the organization of phenomena in terms of dynamic configurations, independent of the nature, type, or spatial and temporal scale of the elements of the system. In medicine, complex descriptions of diseases and their evolution are daily assessed in clinical settings, which can be thus considered as complex systems exhibiting self-organizing and non-linear features, to be investigated through the identification of dynamic feedback-driven behaviors. In this study, a Systems Thinking (ST) approach is proposed to represent the complexity of the theranostic modalities in the context of the personalized nanomedicine through the setting up of a stock-flow diagram. Specifically, the interconnections between the administration of magnetite NBMs for diagnosis and therapy of tumors are fully identified, emphasizing the role of the feedback loops. The presented approach has revealed its suitability for further application in the medical field. In particular, the obtained stock-flow diagram can be adapted for improving the future knowledge of complex systems in personalized nanomedicine as well as in other nanosafety areas.

Risk Management Framework for Nano-Biomaterials Used in Medical Devices and Advanced Therapy Medicinal Products.

The convergence of nanotechnology and biotechnology has led to substantial advancements in nano-biomaterials (NBMs) used in medical devices (MD) and advanced therapy medicinal products (ATMP). However, there are concerns that applications of NBMs for medical diagnostics, therapeutics and regenerative medicine could also pose health and/or environmental risks since the current understanding of their safety is incomplete. A scientific strategy is therefore needed to assess all risks emerging along the life cycles of these products. To address this need, an overarching risk management framework (RMF) for NBMs used in MD and ATMP is presented in this paper, as a result of a collaborative effort of a team of experts within the EU Project BIORIMA and with relevant inputs from external stakeholders. The framework, in line with current regulatory requirements, is designed according to state-of-the-art approaches to risk assessment and management of both nanomaterials and biomaterials. The collection/generation of data for NBMs safety assessment is based on innovative integrated approaches to testing and assessment (IATA). The framework can support stakeholders (e.g., manufacturers, regulators, consultants) in systematically assessing not only patient safety but also occupational (including healthcare workers) and environmental risks along the life cycle of MD and ATMP. The outputs of the framework enable the user to identify suitable safe(r)-by-design alternatives and/or risk management measures and to compare the risks of NBMs to their (clinical) benefits, based on efficacy, quality and cost criteria, in order to inform robust risk management decision-making.