← Back to Search
Probing The Toxicity Of Nanoparticles: A Unified In Silico Machine Learning Model Based On Perturbation Theory
R. Concu, V. V. Kleandrova, A. Speck-Planche, M. N. Cordeiro
Published 2017 · Chemistry, Medicine
Download PDFAnalyze on Scholarcy
Abstract Nanoparticles (NPs) are part of our daily life, having a wide range of applications in engineering, physics, chemistry, and biomedicine. However, there are serious concerns regarding the harmful effects that NPs can cause to the different biological systems and their ecosystems. Toxicity testing is an essential step for assessing the potential risks of the NPs, but the experimental assays are often very expensive and usually too slow to flag the number of NPs that may cause adverse effects. In silico models centered on quantitative structure–activity/toxicity relationships (QSAR/QSTR) are alternative tools that have become valuable supports to risk assessment, rationalizing the search for safer NPs. In this work, we develop a unified QSTR-perturbation model based on artificial neural networks, aimed at simultaneously predicting general toxicity profiles of NPs under diverse experimental conditions. The model is derived from 54,371 NP-NP pair cases generated by applying the perturbation theory to a set of 260 unique NPs, and showed an accuracy higher than 97% in both training and validation sets. Physicochemical interpretation of the different descriptors in the model are additionally provided. The QSTR-perturbation model is then employed to predict the toxic effects of several NPs not included in the original dataset. The theoretical results obtained for this independent set are strongly consistent with the experimental evidence found in the literature, suggesting that the present QSTR-perturbation model can be viewed as a promising and reliable computational tool for probing the toxicity of NPs.
This paper references
Unique cellular interaction of silver nanoparticles: size-dependent generation of reactive oxygen species.
C. Carlson (2008)
Functional analyses of nanoparticle toxicity: a comparative study of the effects of TiO2 and Ag on tomatoes (Lycopersicon esculentum).
U. Song (2013)
Near-infrared Lightmediated Nanoplatforms for Cancer Thermo-chemotherapy and Optical Imaging.
Z. Zhang (2013)
Ecological nanotoxicology: integrating nanomaterial hazard considerations across the subcellular, population, community, and ecosystems levels.
P. Holden (2013)
QSAR and molecular docking techniques for the discovery of potent monoamine oxidase B inhibitors: computer-aided generation of new rasagiline bioisosteres.
A. Speck-Planche (2012)
Acute effects of Fe₂O₃, TiO₂, ZnO and CuO nanomaterials on Xenopus laevis.
Shawna Nations (2011)
Amorphous silica nanoparticles do not induce cytotoxicity, cell transformation or genotoxicity in Balb/3T3 mouse fibroblasts.
Chiara Uboldi (2012)
Chemometrics for QSAR with low sequence homology: Mycobacterial promoter sequences recognition with 2D-RNA entropies
H. González-Díaz (2007)
Computational tool for risk assessment of nanomaterials: novel QSTR-perturbation model for simultaneous prediction of ecotoxicity and cytotoxicity of uncoated and coated nanoparticles under multiple experimental conditions.
V. V. Kleandrova (2014)
Nanoparticles in cancer therapy and diagnosis.
I. Brigger (2002)
A Convergent Synthetic Platform for Single-Nanoparticle Combination Cancer Therapy: Ratiometric Loading and Controlled Release of Cisplatin, Doxorubicin, and Camptothecin
Longyan Liao (2014)
DNA nanotechnology: from sensing and DNA machines to drug-delivery systems.
Chun-hua Lu (2013)
Assessment of the cytotoxicity of aluminium oxide nanoparticles on selected mammalian cells.
E. Radziun (2011)
Phytotoxicity and Biotransformation
Y. Ma (2011)
Palladium nanoparticle enhanced giant photoresponse at LaAlO3/SrTiO3 two-dimensional electron gas heterostructures.
N. Y. Chan (2013)
Exploring the aneugenic and clastogenic potential in the nanosize range: A549 human lung carcinoma cells and amorphous monodisperse silica nanoparticles as models
L. Gonzalez (2010)
Cytotoxicity induced by engineered silver nanocrystallites is dependent on surface coatings and cell types.
Anil K. Suresh (2012)
Effects of surface-modifying ligands on the colloidal stability of ZnO nanoparticle dispersions in in vitro cytotoxicity test media
Dongwook Kwon (2014)
Studies on toxicity of aluminum oxide (Al 2 O 3 ) nanoparticles to microalgae species: Scenedesmus sp. and Chlorella sp.
I. Mohammed (2011)
Toxic Effect of Silver and
M. Ksiazyk (2015)
Ecotoxicity Study of Titania (TiO(2)) NPs on Two
I. M. Sadiq (2011)
Toxicity assessment of zebrafish following exposure to CdTe QDs.
Wei Zhang (2012)
Dependence of QSAR Models on the Selection of Trial Descriptor Sets: A Demonstration Using Nanotoxicity Endpoints of Decorated Nanotubes
Chi-Yu Shao (2013)
Cytotoxicity of surface-functionalized silicon and germanium nanoparticles: the dominant role of surface charges.
Sourav Bhattacharjee (2013)
Silver nanoparticle-induced cytotoxicity in rat brain endothelial cell culture.
Susann Grosse (2013)
How many hidden layers and nodes?
D. Stathakis (2009)
The zerovalent iron nanoparticle causes higher developmental toxicity than its oxidation products in early life stages of medaka fish.
Pei-jen Chen (2013)
CuO nanoparticle interaction with human epithelial cells: cellular uptake, location, export, and genotoxicity.
Z. Wang (2012)
Effects of four types of hydroxyapatite nanoparticles with different nanocrystal morphologies and sizes on apoptosis in rat osteoblasts
Zhengli Xu (2012)
Hydroxyapatite nano and microparticles: correlation of particle properties with cytotoxicity and biostability.
M. Motskin (2009)
Toxicity of nanoparticulate and bulk ZnO, Al2O3 and TiO2 to the nematode Caenorhabditis elegans.
H. Wang (2009)
General theory for multiple input-output perturbations in complex molecular systems. 1. Linear QSPR electronegativity models in physical, organic, and medicinal chemistry.
H. González-Díaz (2013)
Oxidative stress mediated apoptosis induced by nickel ferrite nanoparticles in cultured A549 cells.
M. Ahamed (2011)
Particle size, surface charge and concentration dependent ecotoxicity of three organo-coated silver nanoparticles: comparison between general linear model-predicted and observed toxicity.
Thilini Silva (2014)
Ecotoxic Effect of Photocatalytic Active Nanoparticles (TiO2) on Algae and Daphnids (8 pp)
K. Hund-Rinke (2006)
Multimodal action and selective toxicity of zerovalent iron nanoparticles against cyanobacteria.
B. Marsálek (2012)
Cytotoxicity and morphological transforming potential of cobalt nanoparticles, microparticles and ions in Balb/3T3 mouse fibroblasts: an in vitro model
E. Sabbioni (2014)
Toxicity of nanoparticles of ZnO, CuO and TiO2 to yeast Saccharomyces cerevisiae.
K. Kasemets (2009)
Acute toxicity of cerium oxide, titanium oxide and iron oxide nanoparticles using standardized tests
A. García (2011)
Toxicity of nanosized and bulk ZnO, CuO and TiO2 to bacteria Vibrio fischeri and crustaceans Daphnia magna and Thamnocephalus platyurus.
M. Heinlaan (2008)
SiO2 nanoparticles induce cytotoxicity and protein expression alteration in HaCaT cells
X. Yang (2009)
In vitro toxicity of silica nanoparticles in human lung cancer cells.
W. Lin (2006)
Ceriodaphnia dubia as a Potential Bio-Indicator for Assessing Acute Aluminum Oxide Nanoparticle Toxicity in Fresh Water Environment
Sunandan Pakrashi (2013)
Stepwise Embryonic Toxicity of Silver Nanoparticles on Oryzias latipes
J. Cho (2013)
Bio-active engineered 50 nm silica nanoparticles with bone anabolic activity: therapeutic index, effective concentration, and cytotoxicity profile in vitro.
Shin-woo Ha (2014)
Predictive Toxicology of cobalt ferrite nanoparticles: comparative in-vitro study of different cellular models using methods of knowledge discovery from data
Limor Horev-Azaria (2013)
Acute toxicities of six manufactured nanomaterial suspensions to Daphnia magna
Xiaoshan Zhu (2009)
Toxicity of ZnO and CuO nanoparticles to ciliated protozoa Tetrahymena thermophila.
M. Mortimer (2010)
Using nano-QSAR to predict the cytotoxicity of metal oxide nanoparticles.
T. Puzyn (2011)
Species-specific toxicity of copper nanoparticles among mammalian and piscine cell lines
Lan Song (2014)
Toxicity of Metal Oxide Nanoparticles in Mammalian Cells
H. Jeng (2006)
Organic field-effect transistor memory devices using discrete ferritin nanoparticle-based gate dielectrics.
B. Kim (2013)
Cytotoxicity of silica nanoparticles on HaCaT cells
H. Liang (2014)
A sinter-resistant catalytic system fabricated by maneuvering the selectivity of SiO2 deposition onto the TiO2 surface versus the Pt nanoparticle surface.
P. Lu (2013)
Size-dependent toxicity and cell interaction mechanisms of gold nanoparticles on mouse fibroblasts.
R. Coradeghini (2013)
Chemicool Periodic Table
D. D. Hsu (2013)
Organ biodistribution, clearance, and genotoxicity of orally administered zinc oxide nanoparticles in mice
Ching-Hao Li (2012)
Modeling biological activities of nanoparticles.
V. Epa (2012)
Statistics : methods and applications : a comprehensive reference for science, industry, and data mining
T. Hill (2006)
Differential cytotoxic effects of gold nanoparticles in different mammalian cell lines.
P. J. Chueh (2014)
Catalysis by metal nanoparticles supported on functional organic polymers
M. Králik (2001)
Toxicity Assessment of Iron Oxide Nanoparticles in Zebrafish (Danio rerio) Early Life Stages
Xiaoshan Zhu (2012)
Novel application of the CORAL software to model cytotoxicity of metal oxide nanoparticles to bacteria Escherichia coli.
A. Toropov (2012)
Exposure to Cerium Dioxide Nanoparticles Differently Affect Swimming Performance and Survival in Two Daphnid Species
Ester Artells (2013)
Classification NanoSAR development for cytotoxicity of metal oxide nanoparticles.
R. Liu (2011)
Computational ecotoxicology: simultaneous prediction of ecotoxic effects of nanoparticles under different experimental conditions.
V. V. Kleandrova (2014)
Ecotoxicity study of titania (TiO₂) NPs on two microalgae species: Scenedesmus sp. and Chlorella sp.
I. Sadiq (2011)
Genotoxic potential of copper oxide nanoparticles in human lung epithelial cells.
M. Ahamed (2010)
y-Randomization and Its Variants in QSPR/QSAR
C. Rücker (2007)
Phytotoxicity of nanoparticles: inhibition of seed germination and root growth.
D. Lin (2007)
Influence of the surface coating on the cytotoxicity, genotoxicity and uptake of gold nanoparticles in human HepG2 cells
S. Fraga (2013)
Toxicity and stability of silver nanoparticles to the green alga Pseudokirchneriella subcapitata in boreal freshwater samples and growth media
Meri Tuominen (2013)
Silver nanoparticles exert a long-lasting antiproliferative effect on human keratinocyte HaCaT cell line.
Caterina Zanette (2011)
Toxic Effect of Silver and Platinum Nanoparticles Toward the Freshwater Microalga Pseudokirchneriella subcapitata
M. Książyk (2015)
Nano-quantitative structure-activity relationship modeling using easily computable and interpretable descriptors for uptake of magnetofluorescent engineered nanoparticles in pancreatic cancer cells.
Supratik Kar (2014)
Effects of rare earth oxide nanoparticles on root elongation of plants.
Yuhui Ma (2010)
Toxicity of gold-nanoparticles: Synergistic effects of shape and surface functionalization on micromotility of epithelial cells
M. Tarantola (2011)
Probing surface band bending of surface-engineered metal oxide nanowires.
Chengying Chen (2012)
STATISTICA. Data analysis software system
Nano-SAR development for bioactivity of nanoparticles with considerations of decision boundaries.
R. Liu (2013)
Nickel oxide nanoparticles exert cytotoxicity via oxidative stress and induce apoptotic response in human liver cells (HepG2).
M. Ahamed (2013)
Toxicity and bioaccumulation of TiO2 nanoparticle aggregates in Daphnia magna.
Xiaoshan Zhu (2010)
Loading metal nanostructures on cotton fabrics as recyclable catalysts.
B. Yang (2013)
Oxidation state and symmetry of magnesia-supported Pd13O(x) nanocatalysts influence activation barriers of CO oxidation.
M. Moseler (2012)
Differential stability of lead sulfide nanoparticles influences biological responses in embryonic zebrafish
Lisa Truong (2010)
Oxidative Stress Mediated Apoptosis Induced by Nickel Ferrite Nanoparticles in Cultured A549
M. Ahamed (2011)
Acute Effects of Fe(2
S. Nations (2011)
Polyvinyl alcohol functionalized cobalt ferrite nanoparticles for biomedical applications
A. B. Salunkhe (2013)
Toxic response of nickel nanoparticles in human lung epithelial A549 cells.
M. Ahamed (2011)
Comparative toxicity of several metal oxide nanoparticle aqueous suspensions to Zebrafish (Danio rerio) early developmental stage
Xiaoshan Zhu (2008)
Guti errez. 2002–2004
E. Estrada (2004)
Comparison of the toxicity of silver, gold and platinum nanoparticles in developing zebrafish embryos
P. Asharani (2011)
Toxicity assessments of multisized gold and silver nanoparticles in zebrafish embryos.
Ofek Bar-Ilan (2009)
The planar parabolic optical antenna.
David T. Schoen (2013)
Biotoxicity of nickel oxide nanoparticles and bio-remediation by microalgae Chlorella vulgaris.
N. Gong (2011)
Biomedical applications of distally controlled magnetic nanoparticles.
J. Corchero (2009)
Effects of particle composition and species on toxicity of metallic nanomaterials in aquatic organisms.
R. J. Griffitt (2008)
In vitro toxicity of nanoparticles in BRL 3A rat liver cells.
S. Hussain (2005)
Upper bounds on the number of hidden neurons in feedforward networks with arbitrary bounded nonlinear activation functions
G. Huang (1998)
Small-sample precision of ROC-related estimates
B. Hanczar (2010)
In vitro toxicity of iron oxide nanoparticle: oxidative damages on Hep G2 cells.
L. Sadeghi (2015)
Zinc ferrite nanoparticles activate IL-1b, NFKB1, CCL21 and NOS2 signaling to induce mitochondrial dependent intrinsic apoptotic pathway in WISH cells.
Q. Saquib (2013)
Cytotoxicity and genotoxicity caused by yttrium oxide nanoparticles in HEK293 cells
Vellaisamy Selvaraj (2014)
Cytotoxicity in the age of nano: the role of fourth period transition metal oxide nanoparticle physicochemical properties.
C. C. Chusuei (2013)
Comparative toxicity of nanoparticulate ZnO, bulk ZnO, and ZnCl2 to a freshwater microalga (Pseudokirchneriella subcapitata): the importance of particle solubility.
N. Franklin (2007)
Toxicity of CdTe quantum dots on yeast Saccharomyces cerevisiae.
Xiaole Han (2012)
Phytotoxicity and biotransformation of La2O3 nanoparticles in a terrestrial plant cucumber (Cucumis sativus)
Yuhui Ma (2011)
Computer-aided nanotoxicology: assessing cytotoxicity of nanoparticles under diverse experimental conditions by using a novel QSTR-perturbation approach.
F. Luan (2014)
Quantitative nanostructure-activity relationship modeling.
D. Fourches (2010)
Statistics; methods and applications
J. Griffin (1962)
Studies on toxicity of aluminum oxide (Al2O3) nanoparticles to microalgae species: Scenedesmus sp. and Chlorella sp.
I. Sadiq (2011)
Near-infrared light-mediated nanoplatforms for cancer thermo-chemotherapy and optical imaging.
Zhenjiang Zhang (2013)
This paper is referenced by
New Mechanistic Insights on Carbon Nanotubes Nanotoxicity Using Isolated Submitochondrial Particles, Molecular Docking, and Nano-QSTR Approaches
Michael González-Durruthy (2020)
Practices and Trends of Machine Learning Application in Nanotoxicology
Irini Furxhi (2020)
Nanotoxicology data for in silico tools: a literature review
Irini Furxhi (2020)
Multi-scale QSAR Approach for Simultaneous Modeling of Ecotoxic Effects of Pesticides
A. Speck-Planche (2020)
Nanotechnology-Based Drug Delivery, Metabolism and Toxicity.
Pooja Malaviya (2020)
Nano-(Q)SAR for Cytotoxicity Prediction of Engineered Nanomaterials
A. Buglak (2019)
Machine learning prediction of nanoparticle in vitro toxicity: A comparative study of classifiers and ensemble-classifiers using the Copeland Index.
Irini Furxhi (2019)
Computational models for the assessment of manufactured nanomaterials: Development of model reporting standards and mapping of the model landscape
L. Lamon (2019)
Predicting the cytotoxicity of disinfection by-products to Chinese hamster ovary by using linear quantitative structure–activity relationship models
Li-Tang Qin (2019)
Biohazards of Nanomaterials
Priyanka Maurya (2020)
QSAR modelling: a therapeutic patent review 2010-present
A. K. Halder (2018)
Investigation of iron oxide nanoparticle cytotoxicity in relation to kidney cells: A mathematical modeling of data mining.
Fatemeh Hataminia (2019)
Nanoinformatics in Drug Delivery
Hagit Sason (2019)
Got to Write a Classic: Classical and Perturbation-Based QSAR Methods, Machine Learning, and the Monitoring of Nanoparticle Ecotoxicity
Ana S. Moura (2020)
Evaluating the cytotoxicity of a large pool of metal oxide nanoparticles to Escherichia coli: Mechanistic understanding through In Vitro and In Silico studies.
Supratik Kar (2020)
Cytotoxicity of nanoparticles - Are the size and shape only matters? or the media parameters too?: a study on band engineered ZnS nanoparticles and calculations based on equivolume stress model
Manikanta Bayal (2019)
Artificial Intelligence and Machine Learning in Computational Nanotoxicology: Unlocking and Empowering Nanomedicine.
A. Singh (2020)
Development of Deep Learning Models for Predicting the Effects of Exposure to Engineered Nanomaterials on Daphnia magna.
P. Karatzas (2020)
Pollutants in Organic Chemistry & Medicinal Chemistry Education Laboratory. Experimental and Machine Learning Studies.
Iker Montes-Bageneta (2020)
Use of the index of ideality of correlation to improve models of eco-toxicity
A. Toropova (2018)
In silico profiling nanoparticles: predictive nanomodeling using universal nanodescriptors and various machine learning approaches.
Xiliang Yan (2019)
Whether The Validation Of The Predictive Potential Of Toxicity Models Is Solved Task?
A. Toropova (2019)
Importance of Choosing Relevant Biological End Points To Predict Nanoparticle Toxicity with Computational Approaches for Human Health Risk Assessment.
V. Forest (2019)
Understanding the Interaction of Nanopesticides with Plants
E. F. Santiago (2020)
Role of Artificial Intelligence and Machine Learning in Nanosafety.
D. Winkler (2020)
In silico prediction of drug-induced developmental toxicity by using machine learning approaches
H. Zhang (2019)
Risk assessment of heterogeneous TiO2-based engineered nanoparticles (NPs): a QSTR approach using simple periodic table based descriptors
J. Roy (2019)
Predicting In Vitro Neurotoxicity Induced by Nanoparticles Using Machine Learning
Irini Furxhi (2020)
Application of Bayesian networks in determining nanoparticle-induced cellular outcomes using transcriptomics
Irini Furxhi (2019)
Nanopesticides: From Research and Development to Mechanisms of Action and Sustainable Use in Agriculture
V. L. S. S. Castro (2020)
A unified in silico model based on perturbation theory for assessing the genotoxicity of metal oxide nanoparticles.
A. K. Halder (2019)
Second generation periodic table-based descriptors to encode toxicity of metal oxide nanoparticles to multiple species: QSTR modeling for exploration of toxicity mechanisms
P. De (2018)See more