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Effect of biodegradability on CXCR4 antagonism, transfection efficacy and antimetastatic activity of polymeric Plerixafor

Paper ID Volume ID Publish Year Pages File Format Full-Text
6075 457 2014 8 PDF Available
Title
Effect of biodegradability on CXCR4 antagonism, transfection efficacy and antimetastatic activity of polymeric Plerixafor
Abstract

Chemokine receptor CXCR4 and its sole ligand SDF-1 are key players in regulating cancer cell invasion and metastasis. Plerixafor (AMD3100) is a small-molecule CXCR4 antagonist that prevents binding of SDF-1 to CXCR4 and has potential in prevention of cancer metastasis. This study investigates the influence of biodegradability of a recently reported polymeric Plerixafor (PAMD) on CXCR4 antagonism, antimetastatic activity, and transfection efficacy of PAMD polyplexes with plasmid DNA. We show that PAMD exhibits CXCR4 antagonism and inhibition of cancer cell invasion in vitro regardless of its biodegradability. Biodegradable PAMD showed considerably enhanced transfection efficiency and decreased cytotoxicity when compared with the non-degradable PAMD. Despite similar CXCR4 antagonism in vitro, only biodegradable PAMD displayed antimetastatic activity in experimental lung metastasis model in vivo.

Keywords
CXCR4; Metastasis; Gene delivery; Polyplexes; Bioreducible polycation
First Page Preview
Effect of biodegradability on CXCR4 antagonism, transfection efficacy and antimetastatic activity of polymeric Plerixafor
Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 35, Issue 21, July 2014, Pages 5572–5579
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering