Literature DB >> 24726746

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

Jing Li1, David Oupický2.   

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.
Copyright © 2014 Elsevier Ltd. All rights reserved.

Entities:  

Keywords:  Bioreducible polycation; CXCR4; Gene delivery; Metastasis; Polyplexes

Mesh：

Substances：

Year:  2014        PMID： 24726746      PMCID： PMC4038967          DOI： 10.1016/j.biomaterials.2014.03.047

Source DB:  PubMed          Journal:  Biomaterials        ISSN： 0142-9612            Impact factor:   12.479


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