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

Research output: Contribution to journalArticle

29 Scopus citations

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 invitro 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 invitro, only biodegradable PAMD displayed antimetastatic activity in experimental lung metastasis model invivo.

Original languageEnglish (US)
Pages (from-to)5572-5579
Number of pages8
JournalBiomaterials
Volume35
Issue number21
DOIs
StatePublished - Jul 2014

    Fingerprint

Keywords

  • Bioreducible polycation
  • CXCR4
  • Gene delivery
  • Metastasis
  • Polyplexes

ASJC Scopus subject areas

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

Cite this