Potential toxicity of dental nanomaterials to the central nervous system

Dear editor

It was enlightening to read this comprehensive review of dental nanomaterials toxicity to the central nervous systems (CNSs) by Feng et al¹ published in the International Journal of Nanomedicine. There are many potential applications of nanomaterials in dentistry.² Composite resins have been widely used in restorations of dental caries;³ however, it is estimated that approximately 50% of prepared restorations need to be remade, the secondary caries is one of the most frequent causes of failure,⁴ and the use of nanomaterials could decrease the incidence of these complications. Thus, the application of nanomaterials can bring numerous benefits in dentistry, especially in caries prevention; however, there is an important question about the safety of these materials for the nervous system. In the study by Feng et al¹ a vast array of nanomaterials types and their major applications were outlined.

A strong point of this study¹ is the detailed description of the role of blood–brain barrier (BBB) to prevent potentially harmful substances from entering into the CNS.⁵ This BBB is formed by tight junctions, basement membrane, and glial cells that protect the neurons and glial cells, preventing the passive transport of molecules >500 Da between CNS and blood capillaries.^6,7 However, as discussed by Feng et al¹ some nanomaterials that have been utilized as drug carriers can cross the BBB. This possibility to cross the BBB has important concerns about the use of nanomaterials and possible neurotoxicity, especially in children. Another important point in the paper is the discussion about a complex topic as nanomaterials is comprehensive, but in simple language, which makes it accessible for general dentists and neurologists.

First and foremost, it becomes clear to the reader how faster and more efficient it has been the development and spread of nanoparticles (NPs) than its biosecurity research counterpart. As an example, the authors could not find any study on NPs elimination from the CNS. Moreover, on the exploration of this final via in the metabolism of NPs, the new recent findings regarding a CNS lymphatic system should be considered.⁸ On the other hand, although not entirely understood, the pathways for systemic absorption and CNS distribution of NPs could be reviewed extensively by the authors and this is a major virtue of this study.

Given all the current and potential future impacts to human health, there is a need for the regulatory and governmental agencies to lean over this matter. This could have been better explored in this study. There are some ongoing initiatives from the Food and Drug Administration: its National Center for Toxicological Research is conducting toxicity studies on nanomaterials and the Center for Drug Evaluation and Research has ongoing research projects to identify the limitations of current test methods to assess the quality and safety of NP-based therapeutics.⁹

The main research challenges, as discussed in Figure 5 regarding the existing problems in assessing the neurotoxicity of NPs, could be summarized in three main front lines. Methodological standardization is a must to enable interpretation of results of multiple studies and to allow replicability, an undervalued step for science progress. As the authors demonstrated, standard procedures are still lacking to evaluate NPs toxicity. Second, the process of translating the current knowledge from pre-clinical experiments to human Phase I/II studies is still in its beginning. In this regard, we may have even more incognito after effects in different age groups and/or comorbid conditions. Ultimately, considering that many toxicity effects present on the long-term, to achieve early results with clinical significance, identification of reliable surrogate endpoints will be demanded.