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.
- CXCR4 antagonist
- breast cancer
- siRNA delivery
ASJC Scopus subject areas
- Polymers and Plastics
- Materials Chemistry
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.
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