Effect of Biodegradability on CXCR4 Antagonism, Transfection Efficacy and Antimetastatic Activity of Polymeric Plerixafor

Overview

Journal Biomaterials

Specialty Biomedical Engineering

Date 2014 Apr 15

PMID 24726746

Citations 32

Authors

Jing Li

David Oupicky

Affiliations

Soon will be listed here.

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.

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