Cancer cell-selective promoter recognition accompanies antitumor effect by glucocorticoid receptor-targeted gold nanoparticle.
Nanoparticles, such as gold nanoparticles (GNP), upon convenient modifications perform multi tasks catering to many biomedical applications. However, GNP or any other type of nanoparticles is yet to achieve the feat of intracellular regulation of endogenous genes of choice such as through manipulation of a gene-promoter in a chromosome. As for gene modulation and delivery, GNP (or other nanoparticles) showed only limited gene therapy potential, which relied on the delivery of 'exogenous' genes invoking gene knockdown or replacement. Practically, there are no instances for the nanoparticle-mediated promoter regulation of 'endogenous' genes, more so, as a cancer selective phenomenon. In this regard, we report the development of a simple, easily modifiable GNP-formulation, which promoted/up-regulated the expression of a specific category of 'endogenous' genes, the glucocorticoid responsive genes. This genetic up-regulation was induced in only cancer cells by modified GNP-mediated transcriptional activation of its cytoplasmic receptor, glucocorticoid receptor (GR). Normal cells and their GR remained primarily unperturbed by this GNP-formulation. The most potent gene up-regulating GNP-formulation down-regulated a cancer-specific proliferative signal, phospho-Akt in cancer cells, which accompanied retardation of tumor growth in the murine melanoma model. We show that GR-targeted GNPs may find potential use in the targeting and modulation of genetic information in cancer towards developing novel anticancer therapeutics.
Biomaterials Group, CSIR-Indian Institute of Chemical Technology (CSIR-IICT) Tarnaka, Uppal Road, Hyderabad 500007, India. crpatra@iict.res.in banerjee@iict.res.in rkbanerjee@yahoo.com.
Samaresh
S
Sau
Pritha
P
Agarwalla
Sudip
S
Mukherjee
Indira
I
Bag
Bojja
B
Sreedhar
Manika
M
Pal-Bhadra
Chitta Ranjan
CR
Patra
Rajkumar
R
Banerjee
D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage / Q000737:chemistry; D045744:Cell Line, Tumor; D003907:Dexamethasone / Q000008:administration & dosage* / Q000737:chemistry; D004058:Diffusion; D018390:Gene Targeting / Q000379:methods; D006046:Gold / Q000737:chemistry; D006801:Humans; D053768:Metal Nanoparticles / Q000008:administration & dosage / Q000737:chemistry* / Q000648:ultrastructure; D051379:Mice; D053769:Nanocapsules / Q000008:administration & dosage / Q000737:chemistry / Q000648:ultrastructure; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011965:Receptors, Glucocorticoid / Q000235:genetics*; D016896:Treatment Outcome
D018931:Antineoplastic Agents, Hormonal; D053769:Nanocapsules; D011965:Receptors, Glucocorticoid; D006046:Gold; D003907:Dexamethasone