Glucocorticoid receptor-mediated delivery of nano gold–withaferin conjugates for reversal of epithelial-to-mesenchymal transition and tumor regression. (October 2016)

• Record Type: Journal Article
• Authors: Agarwalla, Pritha; Mukherjee, Sudip; Sreedhar, Bojja; Banerjee, Rajkumar
• Is Part Of: Nanomedicine. Volume 11:Number 19(2016)
• Page Start: 2529
• Page End: 2546
• Publication Date: 2016-10
• Subjects: dexamethasone -- EMT reversal -- glucocorticoid receptor -- gold nanoparticle -- tumor regression; Nanotechnology -- Periodicals; Medical technology -- Periodicals; Nanotechnology -- Therapeutic use -- Periodicals; 610.28
• DOI: 10.2217/nnm-2016-0224
• Languages: English
• ISSNs: 1743-5889

Abstract

Aim: To explore the potential of glucocorticoid receptor-targeted nano-gold formulation as antitumor drug sensitizing agent.Materials & 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.Conclusion: 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.