title: Nano-quantitative structure-activity relationship modeling using easily computable and interpretable descriptors for uptake of magnetofluorescent engineered nanoparticles in pancreatic cancer cells.
abstract: As experimental evaluation of the safety of nanoparticles (NPs) is expensive and time-consuming, computational approaches have been found to be an efficient alternative for predicting the potential toxicity of new NPs before mass production. In this background, we have developed here a regression-based nano quantitative structure-activity relationship (nano-QSAR) model to establish statistically significant relationships between the measured cellular uptakes of 109 magnetofluorescent NPs in pancreatic cancer cells with their physical, chemical, and structural properties encoded within easily computable, interpretable and reproducible descriptors. The developed model was rigorously validated internally as well as externally with the application of the principles of Organization for Economic Cooperation and Development (OECD). The test for domain of applicability was also carried out for checking reliability of the predictions. Important fragments contributing to higher/lower cellular uptake of NPs were identified through critical analysis and interpretation of the developed model. Considering all these identified structural attributes, one can choose or design safe, economical and suitable surface modifiers for NPs. The presented approach provides rich information in the context of virtual screening of relevant NP libraries.
authors.affiliation: Drug Theoretics and Cheminformatics Laboratory, Department of Pharmaceutical Technology, Jadavpur University, Kolkata 700032, India.
authors.forename: Supratik
authors.initials: S
authors.lastname: Kar
authors.affiliation: Laboratory of Environmental Chemometrics, Institute for Environmental and Human Health Protection, Faculty of Chemistry, University of Gdańsk, Gdańsk, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Gajewicz
authors.affiliation: Laboratory of Environmental Chemometrics, Institute for Environmental and Human Health Protection, Faculty of Chemistry, University of Gdańsk, Gdańsk, Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Puzyn
authors.affiliation: Drug Theoretics and Cheminformatics Laboratory, Department of Pharmaceutical Technology, Jadavpur University, Kolkata 700032, India. Electronic address: kunalroy_in@yahoo.com.
authors.forename: Kunal
authors.initials: K
authors.lastname: Roy
mesh_terms: D001692:Biological Transport; D019295:Computational Biology; D003198:Computer Simulation; D005456:Fluorescent Dyes; D006801:Humans; D058185:Magnetite Nanoparticles; D008954:Models, Biological; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D021281:Quantitative Structure-Activity Relationship
chemical_list: D005456:Fluorescent Dyes; D058185:Magnetite Nanoparticles
keywords: In silico; Magnetofluorescent; Nano-QSAR; Nanoparticles; OECD