title: A polyvalent aptamer system for targeted drug delivery.
abstract: 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 (≈ 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.
authors.affiliation: State Key Laboratory of Heavy Oil Processing, College of Science, China University of Petroleum, Qingdao 266580, People's Republic of China; Department of Pharmaceutical Sciences, Sue and Bill Gross Stem Cell Research Center and Chao Family Comprehensive Cancer Center, University of California, Irvine, 845 Health Sciences Road, Irvine, CA 92697, USA; Department of Biomedical Engineering, and Edwards Lifesciences Center for Advanced Cardiovascular Technology, University of California, Irvine, 845 Health Sciences Road, Irvine, CA 92697, USA.
authors.forename: Zhiqing
authors.initials: Z
authors.lastname: Zhang
authors.forename: M Monsur
authors.initials: MM
authors.lastname: Ali
authors.forename: Mark A
authors.initials: MA
authors.lastname: Eckert
authors.forename: Dong-Ku
authors.initials: DK
authors.lastname: Kang
authors.forename: Yih Yang
authors.initials: YY
authors.lastname: Chen
authors.forename: Leonard S
authors.initials: LS
authors.lastname: Sender
authors.forename: David A
authors.initials: DA
authors.lastname: Fruman
authors.forename: Weian
authors.initials: W
authors.lastname: Zhao
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D052157:Aptamers, Nucleotide / Q000737:chemistry / Q000378:metabolism*; D001483:Base Sequence; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry / Q000378:metabolism*; D016503:Drug Delivery Systems; D006801:Humans; D007938:Leukemia / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D000903:Antibiotics, Antineoplastic; D052157:Aptamers, Nucleotide; D004337:Drug Carriers; D004317:Doxorubicin
keywords: Aptamer; Cancer; Drug delivery; Leukemia; Multivalency; Rolling circle amplification