期刊
BIOMATERIALS
卷 35, 期 12, 页码 3840-3850出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2014.01.019
关键词
Nucleolin As1411; Liposomes siRNA delivery; Melanomas; Therapeutic effect
资金
- National Basic Research Program of China [2012CB720604, 2012AA022501]
- NSFC projects [20092001]
- New Drug RD [2009ZX09310-001]
BRAF gene mutation is found in more than 60% of malignant melanomas, which are difficult to treat. In this study, a new tumor-targeting liposome was developed to deliver anti-BRAF siRNA (siBraf) for the treatment of melanomas. Nucleolin is overexpressed on the surface of cancer cells. AS1411, an aptamer showing specific binding to nucleolin, was conjugated to PEGylated cationic liposome as the targeting probe ASLP (AS1411 PEG-liposome). The ASLP/siRNA complex was formed through electrostatic interaction between ASLP and siRNA. The binding of A51411 to the surface of PEGylated liposomes was confirmed by gel electrophoresis and capillary electrophoresis. Real-time PCR and Western blot analysis showed that ASLP/siBraf exhibited strong silencing activity of BRAE gene. The much higher accumulation of the siRNA in tumor cells comparing with normal cells indicated that ASLP displayed excellent tumortargeting capability. Notably, ASLP/siBraf showed significant silencing activity in A375 tumor xenograft mice and inhibited the melanoma growth. These results suggested that the new nucleolin-targeted siRNA delivery system by AS1411 may have the potential for the treatment of melanoma. (c) 2014 Elsevier Ltd. All rights reserved.
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