title: Polymeric Plerixafor: effect of PEGylation on CXCR4 antagonism, cancer cell invasion, and DNA transfection.
abstract: OBJECTIVE
  To determine the effect of PEG modification on pharmacologic and gene delivery properties of polymeric CXCR4 antagonist based on Plerixafor.
  
  
  METHODS
  Polymeric Plerixafor (PAMD) was synthesized from Plerixafor (AMD3100) and grafted with different amounts of PEG (2 kDa). CXCR4 antagonism of the synthesized polymers was determined using receptor redistribution assay. Inhibition of cancer cell invasion by the polyplexes of the synthesized polymers was assessed using Boyden-chamber method. Transfection activity of DNA polyplexes formed with the synthesized polymers was evaluated in U2OS osteosarcoma and B16F10 melanoma cells.
  
  
  RESULTS
  Our results demonstrate that modification of PAMD with PEG decreased toxicity of the polymers, while preserving their CXCR4 antagonism. Polyplexes prepared with PEG-PAMD inhibited invasion of cancer cells to an extent similar to the commercial CXCR4 antagonist Plerixafor. Negative effect of PEG on transfection activity of PEG-PAMD polyplexes could be overcome by using polyplexes formulated with a mixture of PAMD and PEG-PAMD.
  
  
  CONCLUSIONS
  Modification of PAMD with PEG is a viable strategy to preserve the desirable CXCR4 antagonism and ability to inhibit cancer cell invasion of PAMD, while improving safety and colloidal stability of the PAMD polyplexes.
authors.affiliation: Center for Drug Delivery and Nanomedicine Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, Nebraska, 68198, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.forename: David
authors.initials: D
authors.lastname: Oupický
mesh_terms: D001596:Benzylamines; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical; D002850:Chromatography, Gel; D000080027:Cyclams; D004247:DNA / Q000235:genetics*; D004996:Ethidium / Q000737:chemistry; D006571:Heterocyclic Compounds / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D009361:Neoplasm Invasiveness; D014677:Pharmaceutical Vehicles; D011092:Polyethylene Glycols; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors*; D014162:Transfection
chemical_list: D001596:Benzylamines; D000080027:Cyclams; D006571:Heterocyclic Compounds; D014677:Pharmaceutical Vehicles; D019718:Receptors, CXCR4; D011092:Polyethylene Glycols; D004247:DNA; D004996:Ethidium; C088327:plerixafor