EGF-conjugated bio-safe luteolin gold nanoparticles induce cellular toxicity and cell death mediated by site-specific rapid uptake in human triple negative breast cancer cells

World Health Organization listed breast cancer as the most prevalent form of cancer in recent times. Triple negative breast cancer is its deadliest sub-type characterized by high rate of metastasis and poor prognosis, as it lacks three important therapeutic targets like progesterone, estrogen and HER-2 receptors. This fatal variant exhibit over-expressed epidermal growth factor receptor in 45-70% of infected patients. The present work explores a strategy to target this receptor with flavonoid (luteolin)-conjugated gold nanoparticles synthesized through a facile and fast ultra-sonication assisted route. Synthesized nanoparticles exhibited a diameter of 30.23 +/- 9.96 nm in TEM and possessed high stability as suggested from zeta potential of -38.1 +/- 1.49 mV. The particles showed a characteristic plasmonic resonance at 541 nm measured in UV-Vis spectroscopy. Spherical particles with face centered cubic crystalline structure were observed through HR-TEM, SAED and XRD analysis. Synthesized nanoparticles exhibited significant cytotoxicity (IC50 value of 2 mu g/mL) and induced cell death in MDA-MB-231 TNBC cells. Confocal microscopy confirmed rapid localization of targeted nanoparticles in the nucleus of cancer cells leading to its improved performance. Cell cycle and apoptosis evaluations divulged the occurrence of both necrotic and apoptotic cell death following accumulation of MDA-MB-231 cells in sub-G1 phases. Interestingly nanoparticles were cytocompatible with non-malignant NIH-3T3 cells supporting its clinical promise as a biosafe formulation. The work reflects the first report of Luteolin-conjugated bio-safe gold nanoparticles as targeted therapeutics against triple negative breast cancer.

Automated summary

The World Health Organization has identified breast cancer as the most common form of cancer in recent times. Triple negative breast cancer, the deadliest sub-type, is characterized by a high rate of metastasis and poor prognosis due to the lack of progesterone, estrogen, and HER-2 receptors. This study explores the use of flavonoid-conjugated gold nanoparticles as targeted therapeutics against this subtype.