Openly accessible

Characterization and molecular mechanism of peptide-conjugated gold nanoparticle inhibiting p53-HDM2 interaction in retinoblastoma

Kalmodia, Sushma, Parameswaran, Sowmya, Ganapathy, Kalaivani, Yang, Wenrong, Barrow, Colin, Kanwar, Jagat, Roy, Kislay, Vasudevan, Madavan, Kulkarni, Kirti, Elchuri, Sailaja V. and Krishnakumar, Subramanian 2017, Characterization and molecular mechanism of peptide-conjugated gold nanoparticle inhibiting p53-HDM2 interaction in retinoblastoma, Molecular therapy - nucleic acids, vol. 9, pp. 349-364, doi: 10.1016/j.omtn.2017.10.012.

Attached Files
Name Description MIMEType Size Downloads
kalmodia-characterizationandmolec-2017.pdf Published version application/pdf 3.51MB 9

Title Characterization and molecular mechanism of peptide-conjugated gold nanoparticle inhibiting p53-HDM2 interaction in retinoblastoma
Author(s) Kalmodia, Sushma
Parameswaran, Sowmya
Ganapathy, Kalaivani
Yang, WenrongORCID iD for Yang, Wenrong orcid.org/0000-0001-8815-1951
Barrow, ColinORCID iD for Barrow, Colin orcid.org/0000-0002-2153-7267
Kanwar, JagatORCID iD for Kanwar, Jagat orcid.org/0000-0003-3728-9568
Roy, Kislay
Vasudevan, Madavan
Kulkarni, Kirti
Elchuri, Sailaja V.
Krishnakumar, Subramanian
Journal name Molecular therapy - nucleic acids
Volume number 9
Start page 349
End page 364
Total pages 16
Publisher Elsevier
Place of publication Amsterdam, The Netherlands
Publication date 2017-12-15
ISSN 2162-2531
Keyword(s) apoptosis
cell cycle
gene expression
gold nanoparticles
human double minute 2
in silico
molecular mechanism
p53
peptide
retinoblastoma
Science & Technology
Life Sciences & Biomedicine
Medicine, Research & Experimental
Research & Experimental Medicine
DRUG-DELIVERY
INTRAARTERIAL CHEMOTHERAPY
CANCER-THERAPY
P53 PATHWAY
MDM2
SURFACE
STABILITY
PROTEIN
CELLS
CHEMOREDUCTION
Summary Inhibition of the interaction between p53 and HDM2 is an effective therapeutic strategy in cancers that harbor a wild-type p53 protein such as retinoblastoma (RB). Nanoparticle-based delivery of therapeutic molecules has been shown to be advantageous in localized delivery, including to the eye, by overcoming ocular barriers. In this study, we utilized biocompatible gold nanoparticles (GNPs) to deliver anti-HDM2 peptide to RB cells. Characterization studies suggested that GNP-HDM2 was stable in biologically relevant solvents and had optimal cellular internalization capability, the primary requirement of any therapeutic molecule. GNP-HDM2 treatment in RB cells in vitro suggested that they function by arresting RB cells at the G2M phase of the cell cycle and initiating apoptosis. Analysis of molecular changes in GNP-HDM2-treated cells by qRT-PCR and western blotting revealed that the p53 protein was upregulated; however, transactivation of its downstream targets was minimal, except for the PUMA-BCl2 and Bax axis. Global gene expression and in silico bioinformatic analysis of GNP-HDM2-treated cells suggested that upregulation of p53 might presumptively mediate apoptosis through the induction of p53-inducible miRNAs.
Language eng
DOI 10.1016/j.omtn.2017.10.012
HERDC Research category C1 Refereed article in a scholarly journal
ERA Research output type C Journal article
Copyright notice ©2017, The Authors
Free to Read? Yes
Use Rights Creative Commons Attribution Non-Commercial No-Derivatives licence
Persistent URL http://hdl.handle.net/10536/DRO/DU:30105645

Document type: Journal Article
Collections: School of Life and Environmental Sciences
Open Access Collection
Connect to link resolver
 
Unless expressly stated otherwise, the copyright for items in DRO is owned by the author, with all rights reserved.

Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.

Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 0 times in TR Web of Science
Scopus Citation Count Cited 0 times in Scopus
Google Scholar Search Google Scholar
Access Statistics: 119 Abstract Views, 11 File Downloads  -  Detailed Statistics
Created: Thu, 21 Dec 2017, 17:32:36 EST

Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.