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.
authors.affiliation: Center for Drug Delivery and Nanomedicine, Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE 68198, USA; Department of Pharmaceutical Sciences, Wayne State University, Detroit, MI 48202, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: Center for Drug Delivery and Nanomedicine, Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE 68198, USA; Department of Pharmaceutical Sciences, Wayne State University, Detroit, MI 48202, USA. Electronic address: david.oupicky@unmc.edu.
authors.forename: David
authors.initials: D
authors.lastname: Oupický
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D001596:Benzylamines; D055598:Chemical Phenomena; D054377:Chemokine CXCL12 / Q000378:metabolism; D000080027:Cyclams; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D005260:Female; D056945:Hep G2 Cells; D006571:Heterocyclic Compounds / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D010957:Plasmids; D011485:Protein Binding / Q000187:drug effects; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors*; D014162:Transfection
chemical_list: D016588:Anticarcinogenic Agents; D001596:Benzylamines; C515255:CXCL12 protein, human; C527276:CXCR4 protein, human; D054377:Chemokine CXCL12; D000080027:Cyclams; D006571:Heterocyclic Compounds; D019718:Receptors, CXCR4; C088327:plerixafor
keywords: Bioreducible polycation; CXCR4; Gene delivery; Metastasis; Polyplexes
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