Evaluation of Synergistic Anticancer Activity in Novel Multicomponent Combinations Designed to Enhance Selectivity Against Non-Small Cell Lung Cancer Cells

Archil Chirakadze; Nodar Mitagvaria; Neli Makhviladze; Teimuraz Chubinishvili; George Gabisonia; Iuri Migriauli; Ketevan Chakhnashvili; Mikheil Jangavadze; Zanda Bedinashvili; Nodar Sulashvili; Thariq Thahir Kottilingal; Samya Syed; Giorgi Palavandishvili; Khtuna Tserodze; Kakha Gorgadze; Nana khuskivadze; David Aphkhazava

Authors

Archil Chirakadze PhD, Georgian Technical University Institute "Techinform", Tbilisi, Georgia, Georgian Technical University Institute of Cybernetics, Tbilisi, Georgia, Ivane Javakhishvili Tbilisi State University Institute of Physics, Tbilisi, Georgia
Nodar Mitagvaria Ivane Beritasvili Center of Eperimental Biomedicine, Tbilisi, Georgia
Neli Makhviladze Georgian Techical University, Tbilisi, Georgia
Teimuraz Chubinishvili Georgian Techical University, Tbilisi, Georgia
George Gabisonia Alte university, Tbilisi, Georgia
Iuri Migriauli Alte university, Tbilisi, Georgia
Ketevan Chakhnashvili Grigol Robakidze University, Tbilisi, Georgia
Mikheil Jangavadze Aleksandre Natishvili Institute of Morphology, Tbilisi, Georgia, Ivane Javakhishvili Tbilisi State University, Tbilisi, Georgia
Zanda Bedinashvili Aleksandre Natishvili Institute of Morphology, Tbilisi, Georgia, Ivane Javakhishvili Tbilisi State University, Tbilisi, Georgia
Nodar Sulashvili MD, PhD, Doctor of Pharmaceutical and Pharmacological Sciences In Medicine, Invited Lecturer (Professor) of Scientific Research-Skills Center at Tbilisi State Medical University; Professor of Medical and Clinical Pharmacology of International School of Medicine at Alte University; Professor of Pharmacology of Faculty of Medicine at Georgian National University SEU, Associate Affiliated Professor of Medical Pharmacology of Faculty of Medicine at Sulkhan-Saba Orbeliani University; Associate Professor of Medical Pharmacology at School of Medicine at David Aghmashenebeli University of Georgia; Associate Professor of Biochemistry and Pharmacology Direction of School of Health Sciences at the University of Georgia. Associate Professor of Pharmacology of Faculty of Dentistry and Pharmacy at Tbilisi Humanitarian Teaching University; Tbilisi, Georgia; Orcid: https://orcid.org/0000-0002-9005-8577.
Thariq Thahir Kottilingal Caucasus University, Tbilisi, Georgia
Samya Syed University of Georgia, Tbilisi, Georgia
Giorgi Palavandishvili Georgian Techical University, Tbilisi, Georgia
Khtuna Tserodze Georgian Techical University, Tbilisi, Georgia
Kakha Gorgadze Georgian Techical University, Tbilisi, Georgia
Nana khuskivadze Georgian Techical University, Tbilisi, Georgia
David Aphkhazava PhD, Full Professor of Biochemistry at Alte university, Tbilisi, Georgia, Orcid: https://orcid.org/0000-0001-6216-6477

Keywords:

non-small cell lung cancer, combination therapy, synergistic toxicity, selectivity index, zinc oxide nanoparticles, gemcitabine

Abstract

Combination therapy remains one of the most promising strategies in oncology due to its potential to increase therapeutic selectivity while minimizing toxicity to healthy cells. In this study, novel multicomponent formulations containing gemcitabine, potassium citrate, magnesium chloride, zinc oxide (ZnO) nanoparticles, and dimethyl sulfoxide (DMSO) were evaluated for synergistic cytotoxicity against A549 non-small cell lung cancer (NSCLC) cells compared to normal human dermal fibroblasts (NHDF). A total of twelve formulations (eight full combinations and four nanoparticle-only controls) were prepared and evaluated using the MTT assay. Selectivity indices were calculated from experimentally determined LC₅₀ values, and synergy coefficients were derived to quantify interactions between components. The results demonstrate that mixtures containing gemcitabine, ionic modifiers, and ZnO nanoparticles produce a pronounced non-linear increase in selectivity, with synergy peaks occurring at intermediate nanoparticle concentrations. Nanoparticle-only controls displayed minimal selectivity enhancement, indicating that synergistic activity originates from multi-component interactions. These findings support the potential use of multicomponent formulations as selective anticancer agents and highlight the importance of evaluating synergistic relationships during early-stage therapeutic development.

Evaluation of Synergistic Anticancer Activity in Novel Multicomponent Combinations Designed to Enhance Selectivity Against Non-Small Cell Lung Cancer Cells

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