期刊
BIOMACROMOLECULES
卷 19, 期 2, 页码 392-401出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.biomac.7b01487
关键词
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资金
- National Science and Technology Major Project [2017YFA0205400]
- Chinese Ministry of Education
- University of Nebraska Medical Center
- China National Science Foundation [81373983, 81573377]
- China Postdoctoral Science Foundation [2016M601923]
- National Institutes of Health [EB020308]
Chemokine receptor CXCR4 plays an important role in cancer cell invasion and metastasis. Recent findings suggest that anti-VEGF therapies upregulate CXCR4 expression, which contributes to resistance to antiangiogenic therapies. Here, we report the development of novel derivatives of polyethylenimine (PEI) that effectively inhibit CXCR4 while delivering anti-VEGF siRNA. PEI was alkylated with different amounts of a CXCR4-binding cyclam derivative to prepare PEI-C. Modification with the cyclam derivatives resulted in a considerable decrease in cytotoxicity when compared with unmodified PEI. All the PEI-C showed significant CXCR4 antagonism and the ability to inhibit cancer cell invasion. Polyplexes of PEI-C prepared with siVEGF showed effective silencing of the VEGF expression in vitro. In vivo testing in a syngeneic breast cancer model showed promising antitumor and antimetastatic activity of the PEI-C/siVEGF polyplexes. Our data demonstrate the feasibility of using PEI-C as a carrier for simultaneous VEGF silencing and CXCR4 inhibition for enhanced antiangiogenic cancer therapies.
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