期刊
BIOMATERIALS
卷 34, 期 17, 页码 4327-4338出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2013.02.006
关键词
Hyaluronic acid; Imidazole; Buffering; RNA interference; Gene delivery
资金
- National Research Foundation of Korea
- Korean Government (MEST) [2010-0019923, 2012050077]
- Bio & Medical Technology Development Program of the National Research Foundation (NRF)
- National R&D Program for Cancer Control, Ministry for Health and Welfare, Republic of Korea [1020390]
- Korea Health Promotion Institute [1020390] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
We have developed a nanovector consisting of hyaluronic acid (HA) and poly-L-lysine-graft-imidazole (PLI)-based polyplexes containing BcI-xL-specific shRNA-encoding plasmid DNA (HA/PLI/pDNA) for CD44 targeted gastric cancer therapy. The prepared ternary polyplexes have a negative surface charge of -24 mV and a size of approximately 100 nm at an N/P ratio of 5 with HA/PLI molar ratio of 0.03. Gel electrophoresis and cell viability experiments demonstrated that the ternary polyplexes showed high stability and no cytotoxicity due to the anchored HA molecules on the surface of PLI/pDNA binary polyplexes. Selective cancer cell death was achieved by CD44-mediated gene delivery and the internalized gene was effectively escaped from endosomes due to the buffering capacity of imidazole groups in an acidic environment. These nanovectors may be highly efficient gene delivery tools that allow the selective destruction of metastatic gastric cancer cells. (C) 2013 Elsevier Ltd. All rights reserved.
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