title: Development of functional poly(amido amine) CXCR4 antagonists with the ability to mobilize leukocytes and deliver nucleic acids.
abstract: CXCR4 chemokine receptor plays a crucial role in metastatic spread of multiple types of cancer. The present study reports on synthesis of functional polymers based on newly synthesized CXCR4-inhibiting monomers. The resultant linear polymeric CXCR4 antagonists (PCX) show improved ability to inhibit CXCR4 when compared with the monomers. The CXCR4 antagonism provides PCX with the ability to mobilize leukocytes from bone marrow to peripheral blood and to inhibit cancer cell invasion. Due to their cationic nature, PCX can form polyplexes with DNA and mediate efficient transfection. The reported findings validate PCX as promising dual-function polymeric drugs that can deliver therapeutic nucleic acids and improve cancer therapy by simultaneously inhibiting CXCR4 chemokine receptor.
authors.affiliation: Center for Drug Delivery and Nanomedicine, Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Stuart T
authors.initials: ST
authors.lastname: Hazeldine
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.forename: David
authors.initials: D
authors.lastname: Oupický
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D045744:Cell Line, Tumor; D004247:DNA / Q000737:chemistry* / Q000493:pharmacokinetics; D004337:Drug Carriers / Q000737:chemistry* / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D007962:Leukocytes / Q000737:chemistry / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D011073:Polyamines / Q000737:chemistry*; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors*
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; C531249:Poly(amidoamine); D011073:Polyamines; D019718:Receptors, CXCR4; D004247:DNA
keywords: chemokine receptors; gene delivery; polycation; polyplexes