Glucocorticoid receptor-mediated delivery of nano gold-withaferin conjugates for reversal of epithelial-to-mesenchymal transition and tumor regression.
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.
Biomaterials Group, CSIR-Indian Institute of Chemical Technology (CSIR-IICT), Tarnaka, Hyderabad, Telangana 500007, India.|Academy of Scientific & Innovative Research (AcSIR), 2 Rafi Marg, New Delhi 110 001, India.
Pritha
P
Agarwalla
Biomaterials Group, CSIR-Indian Institute of Chemical Technology (CSIR-IICT), Tarnaka, Hyderabad, Telangana 500007, India.|Academy of Scientific & Innovative Research (AcSIR), 2 Rafi Marg, New Delhi 110 001, India.
Sudip
S
Mukherjee
Inorganic & Physical Chemistry Division, CSIR-Indian Institute of Chemical Technology (CSIR-IICT), Tarnaka, Hyderabad, Telangana 500007, India.
Bojja
B
Sreedhar
Biomaterials Group, CSIR-Indian Institute of Chemical Technology (CSIR-IICT), Tarnaka, Hyderabad, Telangana 500007, India.|Academy of Scientific & Innovative Research (AcSIR), 2 Rafi Marg, New Delhi 110 001, India.
Rajkumar
R
Banerjee
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D016466:CHO Cells; D002470:Cell Survival / Q000187:drug effects; D003412:Cricetulus; D003907:Dexamethasone / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D004337:Drug Carriers; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D005260:Female; D006046:Gold / Q000737:chemistry; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D041681:NIH 3T3 Cells; D058726:Nanoconjugates / Q000737:chemistry*; D010316:Particle Size; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D013499:Surface Properties; D014018:Tissue Distribution; D054358:Withanolides / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use
D000970:Antineoplastic Agents; D004337:Drug Carriers; D058726:Nanoconjugates; D011965:Receptors, Glucocorticoid; D054358:Withanolides; D006046:Gold; D003907:Dexamethasone; C009684:withaferin A
EMT reversal; dexamethasone; glucocorticoid receptor; gold nanoparticle; tumor regression