Environmental exposure to nanoparticles (NPs) has significantly increased in the last decades, mostly due to increased environmental pollution and frequent use of NP containing consumer products. Such NPs may enter our body and cause various health-related problems. The brain is a particularly problematic accumulation site due to its physiological and anatomical restrictions, which is reflected also in several population and etiological human studies, which linked increased environmental ND exposure to increased incidence of neurodegenerative and developmental diseases in the recent decades. Several mechanisms of NP neurotoxicity have already been identified, however most focus has been given on exhaust and biomedical NPs and not enough is known especially regarding toxicity of engineered/industrial NPs. The focus of this in vitro study was on analysis of neurotoxicity of different engineered NPs, with which we come into contact in our daily lives; SiO2 NPs, food grade (FG) TiO2 NPs, TiO2 P25 and silver NPs as examples of industrial NPs, and polyacrylic acid (PAA) coated cobalt ferrite NPs as an example of non-toxic, biomedical NPs. All short term exposure experiments (24-72 h) were performed on SH-SY5Y human neuroblastoma cell line in vitro using higher (25-50 µg/ml) as well as lower (2-10 µg/ml), concentrations that are more relevant for in vivo NPs exposure. We show that NPs can cause neurotoxicity through different mechanisms, such as membrane damage, cell cycle interference, ROS formation and accumulation of autophagosomes, depending on their physico-chemical properties and stability in physiological media. Low, in vivo achievable concentrations of NPs induced only minor or no changes in vitro, however prolonged exposure and accumulation in vivo could negatively affect the cells. This was also shown in case of autophagy dysfunction for TiO2 P25 NPs and decrease of cell viability for TiO2 FG NPs, which were only evident after 72 h of incubation. This is especially important since autophagy is an essential mechanism for removal of pathological aggregations of proteins related to neurodegenerative diseases. This paper thus shows the importance of testing also lower NP concentrations, which give us more relevant information regarding possible effects of NP exposure in vivo, as well as the importance of determining the effects of certain toxicity mechanisms also after more than 24 h, which is especially important for in vitro cell models that show slow division rate and slow NP uptake. Low or no division and slow NP uptake can also be expected from neural cells in vivo. Part of the study was also presented on the international conference BioNanoMed [COBISS.SI-ID 12473172]
COBISS.SI-ID: 12841556
Stem cell-based therapeutics is a rapidly developing field associated with a number of clinical challenges. One such challenge lies in the implementation of methods to track stem cells and stem cell-derived cells in experimental animal models and in the living patient. In this review paper we provide an overview of cell tracking in the context of cardiac and neurological disease, focusing on the use of iron oxide-based nanoparticles (IONPs) visualized in vivo using magnetic resonance imaging (MRI). The review covers different available IONP formulations suitable for cell labelling and tracking, approaches for cell labelling and modes of delivery to the brain and heart target tissues. A lot of focus was give also the fate of such NPs in the organism and possible exposure problems, covering the formation of the protein corona and possible immune recognition, internalization of NPs, intracellular trafficking and intracellular fate in relation to the desired imaging applications and toxicity mechanisms with the focus on NP degradation, iron release and metabolism, toxicity and ROS induction, which are all important factors for both suitability and efficacy of NPs for the desired application. The main contribution of this review paper is a thorough literature overview on preclinical and clinical applications of IONPs in cardiac and neurological diseases, which gave important information on the current state of NP development, most promising IONP formulations and potential problems that still need to be addressed. The review paper is an important contribution to the field, since it gives focused overview of the current state of affairs in this fast developing field. Cell labelling and tracking as a diagnostic and treatment tool shows great potential, with several clinical studies especially in neurological diseases and emerging possibilities also in the field of cardiac disease. The approach is relatively safe and feasible, although several issues still need to be addressed, especially regarding sufficient cell loading and labelling specificity. This review paper is a product of collaboration of several experts in their fields, connected through the COST action CA16122 (BIONECA). Through making of this paper, knowledge, ideas and expertise were sheared, establishing and strengthening novel collaborations.
COBISS.SI-ID: 12780372
Magnetic nanoparticles (MNPs) are, due to their specific magnetic properties, suitable for different biomedical applications. The most notable examples are magnetic fluid hyperthermia, visualization and tracking of the cells in vitro and in vivo, and the use of MNPs as delivery platforms for innovative targeted drug-delivery systems. However, despite the different advantages of MNPs, it is necessary to explore their potential undesired effects (e.g., toxicity to cells, tissues and organs, immunotoxicity, immunogenicity and others). The appropriate in vivo and biomimetic in vitro models are an important middle step between in vitro cell culture characterization and optimization of the novel NP formulation and the clinical studies and as such crucial for evaluating the properties and limitations of the multimodal MNPs, which cannot be assessed on simple in vitro cell cultures. The chapter, published in Elsevier’s book Materials for Biomedical Engineering, covers the essential properties and advantages of MNPs designed for biomedical applications, physicochemical and in vitro characterization techniques, interactions between cells and MNPs and of course the advantages, limitations and perspectives of biomimetic in vitro models. Most biomimetic in vitro models have been develop and recognized as a useful and informative step before animal experiments only in the last decade. Adhering to the concept of the Three Rs (replacement, reduction and refinement), such models enable crucial insights into the behavior, toxicity and efficacy of MNPs in contact with target tissues and with these corrections to the MNP design before in vivo experiments, decreasing the need for animal testing to the most promising MNP formulations. This chapter thus contributes to wider recognition of the importance of biomimetic in vitro models and discusses important advantages, disadvantages and considerations to take into account when designing such studies.
COBISS.SI-ID: 34255065