期刊
BIOMATERIALS
卷 34, 期 37, 页码 9728-9735出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2013.08.079
关键词
Aptamer; Rolling circle amplification; Multivalency; Drug delivery; Leukemia; Cancer
资金
- Department of Pharmaceutical Sciences
- Sue and Bill Gross Stem Cell Research Center
- Chao Family Comprehensive Cancer Center at UC Irvine
- University of California, Cancer Research Coordinating Committee
- National Natural Science Foundation of China (NSFC) [51103179]
- Natural Science Foundation of Shandong Province, China [ZR2011BL017]
- Fundamental Research Funds for the Central Universities
- China Scholarship Council [CSC 201206455009]
Poor efficacy and off-target systemic toxicity are major problems associated with current chemotherapeutic approaches to treat cancer. We developed a new form of polyvalent therapeutics that is composed of multiple aptamer units synthesized by rolling circle amplification and physically intercalated chemotherapy agents (termed as Poly-Aptamer-Drug). Using a leukemia cell-binding aptamer and doxorubicin as a model system, we have successfully constructed Poly-Aptamer-Drug systems and demonstrated that the Poly-Aptamer-Drug is significantly more effective than its monovalent counterpart in targeting and killing leukemia cells due to enhanced binding affinity (similar to 40 fold greater) and cell internalization via multivalent effects. We anticipate that our Poly-Aptamer-Drug approach will yield new classes of tunable therapeutics that can be utilized to effectively target and treat cancers while minimizing the side effects of chemotherapy. (C) 2013 Elsevier Ltd. All rights reserved.
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