Cholesterol Modification Enhances Antimetastatic Activity and siRNA Delivery Efficacy of Poly(ethylenimine)-Based CXCR4 Antagonists

Pengkai Wu, Xingping Luo, Hui Wu, Fei Yu, Kaikai Wang, Minjie Sun, David Oupicky

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Chemokine receptor CXC receptor 4 (CXCR4) plays a crucial role in cell invasion and metastasis of multiple types of cancer. Dual-function polymeric CXCR4 antagonists based on cyclam-modified poly(ethylenimine) (C-PEI) have been shown to have potential as nucleic acid delivery vectors and antimetastatic therapeutics in recent studies. How cholesterol modification of C-PEI affects the ability of the polycation to deliver siRNA and inhibit CXCR4 is tested here. It is shown that the C-PEI with the lower content of cholesterol exhibits the highest siRNA transfection efficiency and demonstrates enhanced CXCR4 antagonism and antimetastatic activity in a breast cancer model in vivo. Overall, the cholesterol modification of C-PEI is a viable strategy to achieve efficient delivery of siRNA and simultaneous CXCR4 inhibition for combined antimetastatic therapies is validated by this study.

Original languageEnglish (US)
Article number1800234
JournalMacromolecular Bioscience
Volume18
Issue number11
DOIs
StatePublished - Nov 2018

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Keywords

  • CXCR4 antagonist
  • breast cancer
  • polyethylenimine
  • siRNA delivery

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Biomaterials
  • Polymers and Plastics
  • Materials Chemistry

Cite this

Cholesterol Modification Enhances Antimetastatic Activity and siRNA Delivery Efficacy of Poly(ethylenimine)-Based CXCR4 Antagonists. / Wu, Pengkai; Luo, Xingping; Wu, Hui; Yu, Fei; Wang, Kaikai; Sun, Minjie; Oupicky, David.

In: Macromolecular Bioscience, Vol. 18, No. 11, 1800234, 11.2018.

Research output: Contribution to journalArticle