Cytotoxicity of Nanoparticles Lewinski, Nastassja; Colvin, Vicki; Drezek, Rebekah
Small (Weinheim an der Bergstrasse, Germany),
January 18, 2008, Volume:
4, Issue:
1
Journal Article
Peer reviewed
Human exposure to nanoparticles is inevitable as nanoparticles become more widely used and, as a result, nanotoxicology research is now gaining attention. However, while the number of nanoparticle ...types and applications continues to increase, studies to characterize their effects after exposure and to address their potential toxicity are few in comparison. In the medical field in particular, nanoparticles are being utilized in diagnostic and therapeutic tools to better understand, detect, and treat human diseases. Exposure to nanoparticles for medical purposes involves intentional contact or administration; therefore, understanding the properties of nanoparticles and their effect on the body is crucial before clinical use can occur. This Review presents a summary of the in vitro cytotoxicity data currently available on three classes of nanoparticles. With each of these nanoparticles, different data has been published about their cytotoxicity due to varying experimental conditions as well as differing nanoparticle physiochemical properties. For nanoparticles to move into the clinical arena, it is important that nanotoxicology research uncovers and understands how these multiple factors influence the toxicity of nanoparticles so that their undesirable properties can be avoided.
Nanotoxicology: Nanoparticle safety is a growing concern as commercial use of nanoparticles continues to rise. Several current and potential applications of nanoparticles involve direct human exposure; however, the effects of nanoparticles on human health are still not completely understood. This Review explores the current research published on nanoparticle cytotoxicity.
Nanotechnology‐based cancer treatment approaches potentially provide localized, targeted therapies that aim to enhance efficacy, reduce side effects, and improve patient quality of life. ...Gold‐nanoparticle‐mediated hyperthermia shows particular promise in animal studies, and early clinical testing is currently underway. In this article, the rapidly evolving field of gold nanoparticle thermal therapy is reviewed, highlighting recent literature and describing current challenges to clinical translation of the technology.
Gold‐nanoparticle‐mediated thermal therapies represent a promising technology for clinical cancer applications. To treat murine tumors in vivo, gold nanoparticles are intravenously injected, allowed to accumulate in the tumor, and irradiated with an energy source such as near‐infrared laser light to thermally ablate the tumor. This review highlights recent literature in the field of gold‐nanoparticle‐mediated thermal therapies.
Environment stress is a major threat to the existence of coral reefs and has generated a lot of interest in the coral research community. Under the environmental stress, corals can experience tissue ...loss and/or the breakdown of symbiosis between the cnidarian host and its symbiotic algae causing the coral tissue to appear white as the skeleton can be seen by transparency. Image analysis is a common method used to assess tissue response under the environmental stress. However, the traditional approach is limited by the dynamic nature of the coral-algae symbiosis. Here, we observed coral tissue response in the scleractinian coral, Montipora capricornis, using high frequency image analysis throughout the experiment, as opposed to the typical start/end point assessment method. Color analysis reveals that the process can be divided into five stages with two critical stages according to coral tissue morphology and color ratio. We further explore changes to the morphology of individual polyps by means of the Pearson correlation coefficient and recurrence plots, where the quasi-periodic and nonstationary dynamics can be identified. The recurrence quantification analysis also allows the comparison between the different polyps. Our research provides a detailed visual and mathematical analysis of coral tissue response to environmental stress, which potentially shows universal applicability. Moreover, our approach provides a robust quantitative advancement for improving our insight into a suite of biotic responses in the perspective of coral health evaluation and fate prediction.
Model systems approaches search for commonality in patterns underlying biological diversity and complexity led by common evolutionary paths. The success of the approach does not rest on the species ...chosen but on the scalability of the model and methods used to develop the model and engage research. Fine-tuning approaches to improve coral cell cultures will provide a robust platform for studying symbiosis breakdown, the calcification mechanism and its disruption, protein interactions, micronutrient transport/exchange, and the toxicity of nanoparticles, among other key biological aspects, with the added advantage of minimizing the ethical conundrum of repeated testing on ecologically threatened organisms. The work presented here aimed to lay the foundation towards development of effective methods to sort and culture reef-building coral cells with the ultimate goal of obtaining immortal cell lines for the study of bleaching, disease and toxicity at the cellular and polyp levels. To achieve this objective, the team conducted a thorough review and tested the available methods (i.e. cell dissociation, isolation, sorting, attachment and proliferation). The most effective and reproducible techniques were combined to consolidate culture methods and generate uncontaminated coral cell cultures for ~7 days (10 days maximum). The tests were conducted on scleractinian corals Pocillopora acuta of the same genotype to harmonize results and reduce variation linked to genetic diversity. The development of cell separation and identification methods in conjunction with further investigations into coral cell-type specific metabolic requirements will allow us to tailor growth media for optimized monocultures as a tool for studying essential reef-building coral traits such as symbiosis, wound healing and calcification at multiple scales.
Optimization of extrusion-based bioprinting (EBB) parameters have been systematically conducted through experimentation. However, the process is time- and resource-intensive and not easily ...translatable to other laboratories. This study approaches EBB parameter optimization through machine learning (ML) models trained using data collected from the published literature. We investigated regression-based and classification-based ML models and their abilities to predict printing outcomes of cell viability and filament diameter for cell-containing alginate and gelatin composite bioinks. In addition, we interrogated if regression-based models can predict suitable extrusion pressure given the desired cell viability when keeping other experimental parameters constant. We also compared models trained across data from general literature to models trained across data from one literature source that utilized alginate and gelatin bioinks. The results indicate that models trained on large amounts of data can impart physical trends on cell viability, filament diameter, and extrusion pressure seen in past literature. Regression models trained on the larger dataset also predict cell viability closer to experimental values for material concentration combinations not seen in training data of the single-paper-based regression models. While the best performing classification models for cell viability can achieve an average prediction accuracy of 70%, the cell viability predictions remained constant despite altering input parameter combinations. Our trained models on bioprinting literature data show the potential usage of applying ML models to bioprinting experimental design.
With the ease of gene sequencing and the technology available to study and manipulate non-model organisms, the extension of the methodological toolbox required to translate our understanding of model ...organisms to non-model organisms has become an urgent problem. For example, mining of large coral and their symbiont sequence data is a challenge, but also provides an opportunity for understanding functionality and evolution of these and other non-model organisms. Much more information than for any other eukaryotic species is available for humans, especially related to signal transduction and diseases. However, the coral cnidarian host and human have diverged over 700 million years ago and homologies between proteins in the two species are therefore often in the gray zone, or at least often undetectable with traditional BLAST searches. We introduce a two-stage approach to identifying putative coral homologues of human proteins. First, through remote homology detection using Hidden Markov Models, we identify candidate human homologues in the cnidarian genome. However, for many proteins, the human genome alone contains multiple family members with similar or even more divergence in sequence. In the second stage, therefore, we filter the remote homology results based on the functional and structural plausibility of each coral candidate, shortlisting the coral proteins likely to have conserved some of the functions of the human proteins. We demonstrate our approach with a pipeline for mapping membrane receptors in humans to membrane receptors in corals, with specific focus on the stony coral, P. damicornis. More than 1000 human membrane receptors mapped to 335 coral receptors, including 151 G protein coupled receptors (GPCRs). To validate specific sub-families, we chose opsin proteins, representative GPCRs that confer light sensitivity, and Toll-like receptors, representative non-GPCRs, which function in the immune response, and their ability to communicate with microorganisms. Through detailed structure-function analysis of their ligand-binding pockets and downstream signaling cascades, we selected those candidate remote homologues likely to carry out related functions in the corals. This pipeline may prove generally useful for other non-model organisms, such as to support the growing field of synthetic biology.
Gold nanoparticle-mediated photothermal therapy (PTT) has shown great potential for the treatment of cancer in mouse studies and is now being evaluated in clinical trials. For this therapy, gold ...nanoparticles (AuNPs) are injected intravenously and are allowed to accumulate within the tumor via the enhanced permeability and retention (EPR) effect. The tumor is then irradiated with a near infrared laser, whose energy is absorbed by the AuNPs and translated into heat. While reliance on the EPR effect for tumor targeting has proven adequate for vascularized tumors in small animal models, the efficiency and specificity of tumor delivery
in vivo
, particularly in tumors with poor blood supply, has proven challenging. In this study, we examine whether human T cells can be used as cellular delivery vehicles for AuNP transport into tumors. We first demonstrate that T cells can be efficiently loaded with 45 nm gold colloid nanoparticles without affecting viability or function (e.g. migration and cytokine production). Using a human tumor xenograft mouse model, we next demonstrate that AuNP-loaded T cells retain their capacity to migrate to tumor sites
in vivo
. In addition, the efficiency of AuNP delivery to tumors
in vivo
is increased by more than four-fold compared to injection of free PEGylated AuNPs and the use of the T cell delivery system also dramatically alters the overall nanoparticle biodistribution. Thus, the use of T cell chaperones for AuNP delivery could enhance the efficacy of nanoparticle-based therapies and imaging applications by increasing AuNP tumor accumulation.
The application of established cell viability assays such as the commonly used trypan blue staining method to coral cells is not straightforward due to different culture parameters and different ...cellular features specific to mammalian cells compared to marine invertebrates. Using Pocillopora damicornis as a model, we characterized the autofluorescence and tested different fluorescent dye pair combinations to identify alternative viability indicators. The cytotoxicity of different representative molecules, namely small organic molecules, proteins and nanoparticles (NP), was measured after 24 h of exposure using the fluorescent dye pair Hoechst 33342 and SYTOX orange. Our results show that this dye pair can be distinctly measured in the presence of fluorescent proteins plus chlorophyll. P. damicornis cells exposed for 24 h to Triton-X100, insulin or titanium dioxide (TiO
) NPs, respectively, at concentrations ranging from 0.5 to 100 µg/mL, revealed a LC50 of 0.46 µg/mL for Triton-X100, 6.21 µg/mL for TiO
NPs and 33.9 µg/mL for insulin. This work presents the approach used to customize dye pairs for membrane integrity-based cell viability assays considering the species- and genotype-specific autofluorescence of scleractinian corals, namely: endogenous fluorescence characterization followed by the selection of dyes that do not overlap with endogenous signals.
Coral reefs, among the most diverse ecosystems on Earth, currently face major threats from pollution, unsustainable fishing practices , and perturbations in environmental parameters brought on by ...climate change. Corals also sustain regular wounding from other sea life and human activity. Recent reef restoration practices have even involved intentional wounding by systematically breaking coral fragments and relocating them to revitalize damaged reefs, a practice known as microfragmentation. Despite its importance, very little research has explored the inner mechanisms of wound healing in corals. Some reef-building corals have been observed to initiate an immunological response to wounding similar to that observed in mammalian species. Utilizing prior models of wound healing in mammalian species as the mathematical basis, we formulated a mechanistic model of wound healing, including observations of the immune response and tissue repair in scleractinian corals for the species Pocillopora damicornis. The model consists of four differential equations which track changes in remaining wound debris, number of cells involved in inflammation, number of cells involved in proliferation, and amount of wound closure through re-epithelialization. The model is fit to experimental wound size data from linear and circular shaped wounds on a live coral fragment. Mathematical methods, including numerical simulations and local sensitivity analysis, were used to analyze the resulting model. The parameter space was also explored to investigate drivers of other possible wound outcomes. This model serves as a first step in generating mathematical models for wound healing in corals that will not only aid in the understanding of wound healing as a whole, but also help optimize reef restoration practices and predict recovery behavior after major wounding events.
•Developed model to research cellular dynamics during wound healing in corals.•Mathematical modeling can be used to predict recovery from wounding events in coral.•Model transients matched trends in experimental data for Pocillopora damicornis.•Wound size and shape (linear or circular) can influence healing times.•Model simulations indicate the importance of the inflammatory response in healing.
Little consistency exists in the methodology for toxicological testing of aerosolized nanoparticles used in in vitro, air-interfaced culture (AIC) exposure systems for engineered nanoparticles (ENPs) ...risk-assessment, preventing inter-laboratory comparisons to identify dose thresholds for adverse effects. These inconsistencies result from heterogeneity in particle types, exposure durations, exposure systems, and dose metrics reported. We screened 10,241 studies in the literature for toxicological assessment of ENPs, resulting in 110 publications included after meeting eligibility criteria. In this review, we critically analyzed methodology within these studies to answer whether: (1) the administered dose or the deposited dose correlated better with biological response, (2) a difference existed between various AIC exposure systems when depositing the same dose, (3) consistent results were generated for nanomaterials with similar physico-chemical properties, (4) the deposited dose in vitro correlated to the deposited dose in vivo, and (5) AIC studies reliably modeled acute toxicity in vivo. Methods used in delivering, measuring, and reporting ENP aerosol doses in vitro are summarized. Dosimetry and biological response comparisons of AIC, conventional suspensions, and in vivo exposures are discussed through case studies on silver, zinc oxide, titanium dioxide, and multi-walled carbon nanotube exposures. Finally, based on these findings, recommendations are offered for design of future AIC experiments to aid standardization and comparisons of results.
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