Glucocorticoid receptor-mediated delivery of nano gold-withaferin conjugates for reversal of epithelial-to-mesenchymal transition and tumor regression.
Keywords
Abstract
OBJECTIVE
To explore the potential of glucocorticoid receptor-targeted nano-gold formulation as antitumor drug sensitizing agent.
METHODS
Simultaneous conjugation of gold nanoparticle with thiol-modified dexamethasone, a synthetic glucocorticoid and anticancer drug withaferin A afforded stable gold nanoparticle-modifed dexamethasone-withaferin A nanoconjugate.
RESULTS
This metallic nanoparticle formulation showed glucocorticoid receptor-dependent cancer cell selective cytotoxicity, inhibited growth of aggressive mouse melanoma tumor, reduced mice mortality, while reversing epithelial-to-mesenchymal transition in tumor cells. Same treatment also leads to near-complete downregulation of ABCG2 drug transporter in tumor-associated cells thus attributing it to its drug sensitizing ability.
CONCLUSIONS
The presently synthesized nanoconjugate holds a great promise to sensitize cancer cells to chemotherapeutics and induce epithelial-to-mesenchymal transition reversal in tumor cells preventing metastasis.