Selective activation of antitumor activity of macrophages by the delivery of muramyl dipeptide using a novel polynucleotide-based carrier recognized by scavenger receptors

Srividya, S. ; Roy, R. P. ; Basu, S. K. ; Mukhopadhyay, A. (2000) Selective activation of antitumor activity of macrophages by the delivery of muramyl dipeptide using a novel polynucleotide-based carrier recognized by scavenger receptors Biochemical and Biophysical Research Communications, 268 (3). pp. 772-777. ISSN 0006-291X

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Official URL: http://linkinghub.elsevier.com/retrieve/pii/S00062...

Related URL: http://dx.doi.org/10.1006/bbrc.2000.2216

Abstract

We have shown that muramyl dipeptide (MDP) conjugated to a 10-mer polyguanylic acid (PolyG) is specifically internalized by macrophages through scavenger receptor (SCR)-mediated endocytosis. Macrophages activated by PolyG-MDP displayed about 20-fold higher cytotoxic activity against nonmacrophage tumor cells compared to that elicited by free MDP. The PolyG-MDP was found to trigger the secretion of higher levels of interleukin-6, interleukin-1α, TNF-α, and nitric oxide in comparison to free MDP. Addition of antibodies directed against IL-6 and TNF-α to macrophage culture completely abrogated the tumoricidal response of PolyG-MDP, indicating that these two cytokines are primarily responsible for bioefficacy. This general approach of PolyG as a vehicle may find wide application in the delivery of genes and antisense oligonucleotides to macrophages.

Item Type:Article
Source:Copyright of this article belongs to Elsevier Science.
Keywords:Polynucleotide Carrier; Scavenger Receptor; Macrophage Activation; Muramyl Dipeptide; Antitumor Activity; Cytokines
ID Code:1842
Deposited On:08 Oct 2010 11:58
Last Modified:14 May 2011 11:04

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