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 language | English (US) |
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Article number | 1800234 |
Journal | Macromolecular Bioscience |
Volume | 18 |
Issue number | 11 |
DOIs | |
State | Published - Nov 2018 |
Keywords
- CXCR4 antagonist
- breast cancer
- polyethylenimine
- siRNA delivery
ASJC Scopus subject areas
- Biotechnology
- Bioengineering
- Biomaterials
- Polymers and Plastics
- Materials Chemistry