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Cholesterol Modification Enhances Antimetastatic Activity and siRNA Delivery Efficacy of Poly(ethylenimine)‐Based CXCR4 Antagonists
Author(s) -
Wu Pengkai,
Luo Xingping,
Wu Hui,
Yu Fei,
Wang Kaikai,
Sun Minjie,
Oupicky David
Publication year - 2018
Publication title -
macromolecular bioscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.924
H-Index - 105
eISSN - 1616-5195
pISSN - 1616-5187
DOI - 10.1002/mabi.201800234
Subject(s) - chemistry , in vivo , chemokine receptor , cxcr4 , cxc chemokine receptors , transfection , drug delivery , cxcr4 antagonist , pharmacology , cancer research , biochemistry , receptor , chemokine , medicine , biology , microbiology and biotechnology , organic chemistry , gene
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.