Exploring the Role of Network Pharmacology in Lung Cancer Treatment with Theaflavin-Derived Zinc Nanoparticles

Abstract

Introduction: Lung cancer remains one of the leading causes of global cancer deaths due to tumor heterogeneity, systemic toxicity, and drug resistance. Conventional therapies face limits in specificity and recurrence, thus paving the way for complementary or innovative alternatives. Nanotechnology along with network pharmacology is such an approach. Theaflavin is a polyphenol found in black tea used as medicine for heart disease, cardiovascular diseases,obesity and cancer . when conjugated with zinc nanoparticles (TF-ZnNPs), ensures more adequate bioavailability and stability and targeted anticancer activity. Aim:To study the therapeutic capacity of the zinc nanoparticles of theaflavin in lung cancer using a network pharmacology-aided approach. Materials and Methods: Theaflavin structures were obtained from PubChem while their protein targets were predicted by SwissTargetPrediction. Lung cancer-associated genes were fetched from GeneCards and OMIM. The overlapping targets were represented via Venn diagrams. GO and KEGG pathway enrichment analysis was done using ShinyGO. The PPI networks were constructed with STRING and Cytoscape, with hub genes identified using cytoHubba. Molecular docking was done using AutoDock Vina for binding affinity validation and PyMOL for visualization. Results : Thirty-four overlapping targets were identified. PPI analysis showed TP53, AKT1, EGFR, and MAPK1 as hub genes. GO analysis involved pathways of apoptosis, oxidative stress, and proliferation. KEGG enrichment analysis highlighted PI3K-Akt, MAPK, and Ras signaling. Molecular docking distinguished a strong binding of theaflavin with AKT1 and EGFR, supporting a multitarget-treated role. Conclusion: TF-ZnNPs increase tumor selectivity, solubility, and cellular uptake, offering a multitargeted strategy against lung cancer. These findings present great promise as a novel therapeutic approach, warranting further validation in in vitro and in vivo scenarios aimed toward clinical translation.