The cytotoxicity of nanomaterials: Modeling multiple human cells uptake of functionalized magneto-fluorescent nanoparticles via nano-QSAR.

The vast majority of nanomaterials have attracted an upsurge of interest since their discovery and considerable researches are being carried out about their adverse outcomes for human health and the environment. In this study, two regression-based quantitative structure-activity relationship models for nanoparticles (nano-QSAR) were established to predict the cellular uptakes of 109 functionalized magneto-fluorescent nanoparticles to pancreatic cancer cells (PaCa2) and human umbilical vein endothelial cells (HUVEC) lines, respectively. The improved SMILES-based optimal descriptors encoded with certain easily available physicochemical properties were proposed to describe the molecular structure characteristics of the involved nanoparticles, and the Monte Carlo method was used for calculating the improved SMILES-based optimal descriptors. Both developed nano-QSAR models for cellular uptake prediction provided satisfactory statistical results, with the squared correlation coefficient (R) being 0.852 and 0.905 for training sets, and 0.822 and 0.885 for test sets, respectively. Both models were rigorously validated and further extensively compared to literature models. Predominant physicochemical features responsible for cellular uptake were identified by model interpretation. The proposed models could be reasonably expected to provide guidance for synthesizing or choosing safer, more suitable surface modifiers of desired properties prior to their biomedical applications.