| Epithelial cell adhesion molecule targeted nutlin-3a loaded immunonanoparticles for cancer therapy. | |
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MedLine Citation:
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PMID: 20727991 Owner: NLM Status: In-Process |
Abstract/OtherAbstract:
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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. |
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Authors:
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Manasi Das; Sanjeeb K Sahoo |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-08-19 |
Journal Detail:
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Title: Acta biomaterialia Volume: 7 ISSN: 1878-7568 ISO Abbreviation: Acta Biomater Publication Date: 2011 Jan |
Date Detail:
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Created Date: 2010-11-01 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101233144 Medline TA: Acta Biomater Country: England |
Other Details:
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Languages: eng Pagination: 355-69 Citation Subset: IM |
Copyright Information:
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Copyright © 2010 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved. |
Affiliation:
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Institute of Life Sciences, Bhubaneswar, India. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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