Abstract

The immunological safety of drugs, nanomaterials and contaminants is a central point in the regulatory evaluation and safety monitoring of working and public places and of the environment. In fact, anomalies in immune responses may cause diseases and hamper the physical and functional integrity of living organisms, from plants to human beings. In the case of nanomaterials, many experimental models are used for assessing their immunosafety, some of which have been adopted by regulatory bodies. All of them, however, suffer from shortcomings and approximations, and may be inaccurate in representing real-life responses, thereby leading to incomplete, incorrect or even misleading predictions. Here, we review the advantages and disadvantages of current nanoimmunosafety models, comparing in vivo vs. in vitro models and examining the use of animal vs. human cells, primary vs. transformed cells, complex multicellular and 3D models, organoids and organs-on-chip, in view of implementing a reliable and personalized nanoimmunosafety testing. The general conclusion is that the choice of testing models is key for obtaining reliable predictive information, and therefore special attention should be devoted to selecting the most relevant and realistic suite of models in order to generate relevant information that can allow for safer-by-design nanotechnological developments.

Highlights

  • Nanotechnology and the Use of Engineered NanoparticlesNanotechnology is one of the major technological advancements of the 21st century, with applications in many fields and products

  • It is important to know that the interaction of nanomaterials with the immune system largely occurs with innate immune cells and effector molecules

  • Since immune cells are present in all organs and tissues, advanced immunosafety testing should be performed in systems that represent the microenvironmental conditions of different tissues

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Summary

Nanotechnology and the Use of Engineered Nanoparticles

Nanotechnology is one of the major technological advancements of the 21st century, with applications in many fields and products. Medicines Agency, and are being currently developed for wider applications in cancer therapy, immunotherapeutic approaches and vaccination [13,14,15,16,17,18,19]. Because of their broad applications and abundant presence in our environments, it became urgent to implement a thorough evaluation of the possible toxic effects of ENPs on human and environmental health in order to identify and manage the associated risks [20,21]. Many “safe-by-design” strategies have been developed during the past decades in the attempt to design safer nanomaterials [22]

Immunological Safety
Immunological Safety of ENPs
Immune Recognition and Response
The fouroutcomes possibleof outcomes of nanomaterial–immune system
Drawbacks and Limitations of In Vivo Models
Common Immunological Features across Living Species
In Vitro Immunosafety Models
Transformed Cell Lines
Primary Cells
Good In Vitro Method Practices and Immunoactive Contaminations
Conclusions and Future Perspectives
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