Перспективы развития фундаментальных наук. Т. 2 : Химия

Сборник содержит труды участников XV Международной конференции студентов, аспирантов и молодых учёных «Перспективы развития фундаментальных наук», представленные на секции «Химия». Для студентов, аспирантов, молодых ученых и преподавателей, специализирующихся в области синтеза и изучения свойств функциональных материалов, физико-химических методов исследования материалов, наноматериалов, экологии, органического синтеза, а также катализа и нефтехимии

Intracellular Nanoparticle Coating Stability Determines Nanoparticle Diagnostics Efficacy and Cell Functionality

n/

Genotoxic capacity of Cd/Se semiconductor quantum dots with differing surface chemistries.

Quantum dots (QD) have unique electronic and optical properties promoting biotechnological advances. However, our understanding of the toxicological structure-activity relationships remains limited. This study aimed to determine the biological impact of varying nanomaterial surface chemistry by assessing the interaction of QD with either a negative (carboxyl), neutral (hexadecylamine; HDA) or positive (amine) polymer coating with human lymphoblastoid TK6 cells. Following QD physico-chemical characterisation, cellular uptake was quantified by optical and electron microscopy. Cytotoxicity was evaluated and genotoxicity was characterised using the micronucleus assay (gross chromosomal damage) and the HPRT forward mutation assay (point mutagenicity). Cellular damage mechanisms were also explored, focusing on oxidative stress and mitochondrial damage. Cell uptake, cytotoxicity and genotoxicity were found to be dependent on QD surface chemistry. Carboxyl-QD demonstrated the smallest agglomerate size and greatest cellular uptake, which correlated with a dose dependent increase in cytotoxicity and genotoxicity. Amine-QD induced minimal cellular damage, while HDA-QD promoted substantial induction of cell death and genotoxicity. However, HDA-QD were not internalised by the cells and the damage they caused was most likely due to free cadmium release caused by QD dissolution. Oxidative stress and induced mitochondrial reactive oxygen species were only partially associated with cytotoxicity and genotoxicity induced by the QD, hence were not the only mechanisms of importance. Colloidal stability, nanoparticle (NP) surface chemistry, cellular uptake levels and the intrinsic characteristics of the NPs are therefore critical parameters impacting genotoxicity induced by QD

Cell type-dependent changes in CdSe/ZnS quantum dot uptake and toxic endpoints.

Toxicity of nanoparticles (NPs) is often correlated with the physicochemical characteristics of the materials. However, some discrepancies are noted in in-vitro studies on quantum dots (QDs) with similar physicochemical properties. This is partly related to variations in cell type. In this study, we show that epithelial (BEAS-2B), fibroblast (HFF-1), and lymphoblastoid (TK6) cells show different biological responses following exposure to QDs. These cells represented the 3 main portals of NP exposure: bronchial, skin, and circulatory. The uptake and toxicity of negatively and positively charged CdSe:ZnS QDs of the same core size but with different surface chemistries (carboxyl or amine polymer coatings) were investigated in full and reduced serum containing media following 1 and 3 cell cycles. Following thorough physicochemical characterization, cellular uptake, cytotoxicity, and gross chromosomal damage were measured. Cellular damage mechanisms in the form of reactive oxygen species and the expression of inflammatory cytokines IL-8 and TNF-α were assessed. QDs uptake and toxicity significantly varied in the different cell lines. BEAS-2B cells demonstrated the highest level of QDs uptake yet displayed a strong resilience with minimal genotoxicity following exposure to these NPs. In contrast, HFF-1 and TK6 cells were more susceptible to toxicity and genotoxicity, respectively, as a result of exposure to QDs. Thus, this study demonstrates that in addition to nanomaterial physicochemical characterization, a clear understanding of cell type-dependent variation in uptake coupled to the inherently different capacities of the cell types to cope with exposure to these exogenous materials are all required to predict genotoxicity

Choose your cell model wisely: The in vitro nanoneurotoxicity of differentially coated iron oxide nanoparticles for neural cell labeling

Currently, there is a large interest in the labeling of neural stem cells (NSCs) with iron oxide nanoparticles (IONPs) to allow MRI-guided detection after transplantation in regenerative medicine. For such biomedical applications, excluding nanotoxicity is key. Nanosafety is primarily evaluated in vitro where an immortalized or cancer cell line of murine origin is often applied, which is not necessarily an ideal cell model. Previous work revealed clear neurotoxic effects of PMA-coated IONPs in distinct cell types that could potentially be applied for nanosafety studies regarding neural cell labeling. Here, we aimed to assess if DMSA-coated IONPs could be regarded as a safer alternative for this purpose and how the cell model impacted our nanosafety optimization study. Hereto, we evaluated cytotoxicity, ROS production, calcium levels, mitochondrial homeostasis and cell morphology in six related neural cell types, namely neural stem cells, an immortalized cell line and a cancer cell line from human and murine origin. The cell lines mostly showed similar responses to both IONPs, which were frequently more pronounced for the PMA-IONPs. Of note, ROS and calcium levels showed opposite trends in the human and murine NSCs, indicating the importance of the species. Indeed, the human cell models were overall more sensitive than their murine counterpart. Despite the clear cell type-specific nanotoxicity profiles, our multiparametric approach revealed that the DMSA-IONPs outperformed the PMA-IONPs in terms of biocompatibility in each cell type. However, major cell type-dependent variations in the observed effects additionally warrant the use of relevant human cell models.status: publishe

Coating of Quantum Dots strongly defines their effect on lysosomal health and autophagy

In the last decade the interest in autophagy got an incredible boost and the phenomenon quickly turned into an extensive research field. Interestingly, dysfunction of this cytoplasmic clearance system has been proposed to lie at the root of multiple diseases including cancer. We therefore consider it crucial from a toxicological point of view to investigate if nanomaterials that are developed for biomedical applications interfere with this cellular process. Here, we study the highly promising 'gradient alloyed' Quantum Dots (QDs) that differ from conventional ones by their gradient core composition which allows for better fluorescent properties. We carefully examined the toxicity of two identical gradient alloyed QDs, differing only in their surface coatings, namely 3-mercaptopropionic (MPA) acid and polyethylene glycol (PEG). Next to more conventional toxicological endpoints like cytotoxicity and oxidative stress, we examined the influence of these QDs on the autophagy pathway. Our study shows that the cellular effects induced by QDs on HeLa cells were strongly dictated by the surface coat of the otherwise identical particles. MPA-coated QDs proved to be highly biocompatible as a result of lysosomal activation and ROS reduction, two cellular responses that help the cell to cope with nanomaterial-induced stress. In contrast, PEGylated QDs were significantly more toxic due to increased ROS production and lysosomal impairment. This impairment next results in autophagy dysfunction which likely adds to their toxic effects. Taken together, our study shows that coating QDs with MPA is a better strategy than PEGylation for long term cell tracking with minimal cytotoxicity.status: publishe

The role of intracellular trafficking of CdSe/ZnS QDs on their consequent toxicity profile

Nanoparticle interactions with cellular membranes and the kinetics of their transport and localization are important determinants of their functionality and their biological consequences. Understanding these phenomena is fundamental for the translation of such NPs from in vitro to in vivo systems for bioimaging and medical applications. Two CdSe/ZnS quantum dots (QD) with differing surface functionality (NH2 or COOH moieties) were used here for investigating the intracellular uptake and transport kinetics of these QDs.status: publishe

The effect of nanoparticle degradation on poly(methacrylic acid)-coated quantum dot toxicity: The importance of particle functionality assessment in toxicology

status: publishe

Choose your cell model wisely : the in vitro nanoneurotoxicity of differentially coated iron oxide nanoparticles for neural cell labeling

Currently, there is a large interest in the labeling of neural stem cells (NSCs) with iron oxide nanoparticles (IONPs) to allow MRI-guided detection after transplantation in regenerative medicine. For such biomedical applications, excluding nanotoxicity is key. Nanosafety is primarily evaluated in vitro where an immortalized or cancer cell line of murine origin is often applied, which is not necessarily an ideal cell model. Previous work revealed clear neurotoxic effects of PMA-coated IONPs in distinct cell types that could potentially be applied for nanosafety studies regarding neural cell labeling. Here, we aimed to assess if DMSA-coated IONPs could be regarded as a safer alternative for this purpose and how the cell model impacted our nanosafety optimization study. Hereto, we evaluated cytotoxicity, ROS production, calcium levels, mitochondrial homeostasis and cell morphology in six related neural cell types, namely neural stem cells, an immortalized cell line and a cancer cell line from human and murine origin. The cell lines mostly showed similar responses to both IONPs, which were frequently more pronounced for the PMA-IONPs. Of note, ROS and calcium levels showed opposite trends in the human and murine NSCs, indicating the importance of the species. Indeed, the human cell models were overall more sensitive than their murine counterpart. Despite the clear cell type-specific nanotoxicity profiles, our multiparametric approach revealed that the DMSA-IONPs outperformed the PMA-IONPs in terms of biocompatibility in each cell type. However, major cell type-dependent variations in the observed effects additionally warrant the use of relevant human cell models. Statement of Significance Inorganic nanoparticle (NP) optimization is chiefly performed in vitro. For the optimization of iron oxide (IO)NPs for neural stem cell labeling in the context of regenerative medicine human or rodent neural stem cells, immortalized or cancer cell lines are applied. However, the use of certain cell models can be questioned as they phenotypically differ from the target cell. The impact of the neural cell model on nanosafety remains relatively unexplored. Here we evaluated cell homeostasis upon exposure to PMA- and DMSA-coated IONPs. Of note, the DMSA-IONPs outperformed the PMA-IONPs in each cell type. However, distinct cell type-specific effects were witnessed, indicating that nanosafety should be evaluated in a human cell model that represents the target cell as closely as possible