Integrative In-silico, Network Pharmacology, Pharmacogenomics and In-vitro Evaluation of Fulvestrant-Loaded Zinc Oxide Nanoparticles Targeting HER2 Positive Breast Cancer.

backgroundHER2-positive breast cancer is characterized by the absence of estrogen and progesterone receptors and the overexpression of the HER2 receptor. Existing targeted therapies, leads to side effects like cardiotoxicity, diarrhoea and suffer from poor penetration of the blood brain barrier. Zinc oxide nanoparticles have emerged as a promising drug delivery platform by improving biocompatibility, selective cytotoxicity via reactive oxygen species generation and facilitating effective penetration across biological barriers.

objectiveOur aim was to synthesize and characterize the Fulvestrant-zinc oxide nanoparticles, evaluate its efficacy in-vitro and ascertain its potential as a therapeutic agent for HER2-positive breast cancer.

methodsPharmacogenomics and gene enrichment process were applied to select target by following computational drug design strategy. Based on molecular docking, MMGBSA and molecular dynamics were undertaken to assess the stability. Subsequently, Fulvestrant-zinc oxide nanoparticles were synthesized and characterized using FT-IR, SEM and DSC techniques. In-vitro assessments involved MTT assays and AO/EtBr staining method.

resultsComputational results showed Fulvestrant superior HER2 binding, confirmed by molecular dynamics studies. In vitro studies revealed cytotoxicity and apoptosis.

conclusionThis study highlights the Fulvestrant-zinc oxide nanoparticles as a promising therapeutic intervention for HER2-positive breast cancer. By undergoing computational approaches, Network analysis and pharmacogenomics.