A polyvalent aptamer system for targeted drug delivery

被引：126

作者：

Zhang, Zhiqing ^{[1
,2
,3
,4
,5
]}

Ali, M. Monsur ^{[2
,3
,4
,5
]}

Eckert, Mark A. ^{[2
,3
,4
,5
]}

Kang, Dong-Ku ^{[2
,3
,4
,5
]}

Chen, Yih Yang ^{[2
,3
,4
,5
]}

Sender, Leonard S. ^{[6
,7
]}

Fruman, David A. ^{[8
]}

Zhao, Weian ^{[2
,3
,4
,5
]}

机构：

[1] China Univ Petr, Coll Sci, State Key Lab Heavy Oil Proc, Qingdao 266580, Peoples R China

[2] Univ Calif Irvine, Sue & Bill Gross Stem Cell Res Ctr, Dept Pharmaceut Sci, Irvine, CA 92697 USA

[3] Univ Calif Irvine, Chao Family Comprehens Canc Ctr, Irvine, CA 92697 USA

[4] Univ Calif Irvine, Dept Biomed Engn, Irvine, CA 92697 USA

[5] Univ Calif Irvine, Edwards Lifesci Ctr Adv Cardiovasc Technol, Irvine, CA 92697 USA

[6] Univ Calif Irvine, Dept Med, Irvine, CA 92697 USA

[7] CHOC Childrens Hosp, Hyundai Canc Inst, Orange, CA USA

[8] Univ Calif Irvine, Dept Mol Biol & Biochem, Irvine, CA 92697 USA

来源：

BIOMATERIALS | 2013年 / 34卷 / 37期

基金：

中国国家自然科学基金;

关键词：

Aptamer; Rolling circle amplification; Multivalency; Drug delivery; Leukemia; Cancer; ROLLING-CIRCLE AMPLIFICATION; AMPLIFIED SYNTHESIS; DNA; DOXORUBICIN; NANOPARTICLES; THERAPY; CONJUGATE; TRANSPORT; LIGANDS; PROBES;

D O I：

10.1016/j.biomaterials.2013.08.079

中图分类号：

R318 [生物医学工程];

学科分类号：

0831 ;

摘要：

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.

引用

页码：9728 / 9735

页数：8

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