Predicting Metal Oxide NP Cytotoxicity Using Isalos Analytics

How NovaMechanics enriched a metal oxide nanoparticle dataset with 62 atomistic computational descriptors to build a robust QNAR model that identifies 7 key drivers of cytotoxicity — deployed as a publicly available web service.

Nanomaterials • 2020
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The Challenge

Understanding What Drives Metal Oxide NP Toxicity

Metal oxide nanoparticles are among the most widely produced engineered NPs, used in consumer products from sunscreens to electronics. Yet their ability to cross biological barriers and cause toxic effects makes hazard assessment essential for safe use.

Traditional experimental approaches cannot keep pace with the diversity of engineered NPs. Computational modelling offers a high-throughput alternative, but standard physicochemical descriptors alone are insufficient — atomistic-level structural features are needed to capture the mechanisms driving toxicity.

24
Distinct metal oxide NPs characterised
77
Total descriptors (15 experimental + 62 atomistic)
7
Statistically significant descriptors identified

Our Approach

Combining experimental and atomistic data to build interpretable nanotoxicity models

Retrieve and curate toxicological data

Retrieved cytotoxicity data for 24 metal oxide NPs from the S²NANO database, covering ATP and LDH assays on BEAS-2B and RAW 264.7 cell lines, with 15 physicochemical and structural descriptors.

Enrich with 62 atomistic descriptors

Calculated full-particle atomistic computational descriptors based on crystal structure information alone, using molecular mechanics to derive coordination numbers, energetics, force vectors, and surface properties for each NP.

Build QNAR model on Isalos Analytics

Used the Isalos Analytics Platform to develop a quantitative nanostructure-activity relationship model from the combined 77-descriptor feature space, systematically evaluating statistical significance of each descriptor.

Identify key toxicity drivers

Identified 7 statistically significant descriptors driving cytotoxicity: NP core size, hydrodynamic size, assay type, exposure dose, conduction band energy, metal atom coordination number, and average force vector surface normal component.

Deploy and share through H2020 projects

Published the model as a public web service and integrated it into the NanoSolveIT Integrated Approach to Testing and Assessment (IATA) framework, with data available through the NanoPharos database.

Results at a Glance

49
Citations
High-impact contribution recognised across the nanoinformatics field
62
Atomistic Descriptors
Full-particle computational features from crystal structure alone
7
Key Drivers
Statistically significant descriptors linked to cytotoxicity mechanisms
IATA
Regulatory Framework
Integrated into the NanoSolveIT testing and assessment approach
Public
Web Service
Freely available model for community use and regulatory applications
1,488
Data Points
Comprehensive dataset with enriched atomistic descriptors per NP

Related Publication

Peer-Reviewed Paper

Predicting Cytotoxicity of Metal Oxide Nanoparticles Using Isalos Analytics Platform

Papadiamantis A.G., Jänes J., Voyiatzis E., Sikk L., Burk J., Burk P., Tsoumanis A., Ha M.K., Yoon T.H., Valsami-Jones E., Lynch I., Melagraki G., Täm K., Afantitis A. — Nanomaterials, 2020, 10(10):2017 — DOI: 10.3390/nano10102017