Document Detail


Epithelial cell adhesion molecule targeted nutlin-3a loaded immunonanoparticles for cancer therapy.
MedLine Citation:
PMID:  20727991     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Recently much attention has been given to the anti-cancer drug nutlin-3a, an antagonist of murine double minute 2 (MDM2) that actively inhibits p53-MDM2 interaction. Reactivating p53 function by nutlin-3a thus provides a promising therapeutic strategy for the treatment of cancer. Although nutlin-3a seems a potential candidate in restoring p53 activity, it has many lacunae, toxicity, poor bioavailability, nonspecific delivery, and most importantly it is a substrate of multidrug resistance protein. The objective of the present study is to prepare and characterize nutlin-3a loaded poly(lactide-co-glycolide) (PLGA) nanoparticles (NPs), surface functionalized with epithelial cell adhesion molecule (EpCAM) antibody, with an aim to deliver encapsulated drug in a targeted manner to its site of action and to enhance its therapeutic efficacy many times over. The enhanced cellular uptake of EpCAM antibody conjugated nutlin-3a loaded NPs (EpCAM-nutlin-3a-NPs) over native nulin-3a, nutlin-3a loaded NPs (nutlin-3a-NPs) in HCT116 and A549 cells substantiate the targeting potentiality of conjugated system. IC₅₀ values depicted superior antiproliferative activity of EpCAM-nutlin-3a-NPs over nutlin-3a-NPs and native nutlin-3a in the above studied cell lines. Cell cycle arrest, loss of mitochondrial membrane potential and apoptosis induced by above formulation were confirmed by flow cytometry. Expression of p53, p21, EpCAM, and C-myc proteins involved in cell cycle regulation and apoptosis were investigated by western blotting. The above investigation indicates the enhanced therapeutic ability of EpCAM-nutlin-3a-NPs compared to nutlin-3a or nutlin-3a-NPs. Thus, our results suggest that EpCAM-nutlin-3a-NPs could be a potentially useful drug carrier system for targeted delivery of potent anti-cancer drug nutlin-3a for cancer therapy.
Authors:
Manasi Das; Sanjeeb K Sahoo
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Retracted Publication     Date:  2010-08-19
Journal Detail:
Title:  Acta biomaterialia     Volume:  7     ISSN:  1878-7568     ISO Abbreviation:  Acta Biomater     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2010-11-01     Completed Date:  2011-02-14     Revised Date:  2013-07-01    
Medline Journal Info:
Nlm Unique ID:  101233144     Medline TA:  Acta Biomater     Country:  England    
Other Details:
Languages:  eng     Pagination:  355-69     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
Affiliation:
Institute of Life Sciences, Bhubaneswar, India.
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MeSH Terms
Descriptor/Qualifier:
Antigens, Neoplasm / immunology*
Blotting, Western
Cell Adhesion Molecules / immunology*
Cell Cycle / drug effects
Cell Death / drug effects
Cell Line, Tumor
Coumarins / metabolism
Humans
Imidazoles / pharmacology*
Inhibitory Concentration 50
Intracellular Space / drug effects,  metabolism
Membrane Potential, Mitochondrial / drug effects
Microscopy, Confocal
Nanoparticles / therapeutic use*,  ultrastructure
Neoplasms / therapy*
Particle Size
Physicochemical Phenomena / drug effects
Piperazines / pharmacology*
Polyglactin 910 / pharmacology
Receptors, Cell Surface / metabolism
Solutions
Chemical
Reg. No./Substance:
0/Antigens, Neoplasm; 0/Cell Adhesion Molecules; 0/Coumarins; 0/Imidazoles; 0/Piperazines; 0/Receptors, Cell Surface; 0/Solutions; 0/nutlin 3; 0/tumor-associated antigen GA733; 34346-01-5/Polyglactin 910; A4VZ22K1WT/coumarin
Comments/Corrections
Retraction In:
Acta Biomater. 2013 Jun;9(6):7076   [PMID:  23802319 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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