title: A Synthetic Aptamer-Drug Adduct for Targeted Liver Cancer Therapy.
abstract: AS1411 (previously known as AGRO100) is a 26 nucleotide guanine-rich DNA aptamer which forms a guanine quadruplex structure. AS1411 has shown promising utility as a treatment for cancers in Phase I and Phase II clinical trials without causing major side-effects. AS1411 inhibits tumor cell growth by binding to nucleolin which is aberrantly expressed on the cell membrane of many tumors. In this study, we utilized a simple technique to conjugate a widely-used chemotherapeutic agent, doxorubicin (Dox), to AS1411 to form a synthetic Drug-DNA Adduct (DDA), termed as AS1411-Dox. We demonstrate the utility of AS1411-Dox in the treatment of hepatocellular carcinoma (HCC) by evaluating the targeted delivery of Dox to Huh7 cells in vitro and in a murine xenograft model of HCC.
authors.affiliation: Department of Pathology, Immunology and Laboratory Medicine, College of Medicine, University of Florida, Gainesville, Florida, United States of America.
authors.forename: Thu Le
authors.initials: TL
authors.lastname: Trinh
authors.affiliation: Departments of Chemistry, and Physiology and Functional Genomics, Center for Research at the Bio/Nano Interface, Shands Cancer Center, UF Genetics Institute and McKnight Brain Institute, University of Florida, Gainesville, Florida, United States of America.
authors.forename: Guizhi
authors.initials: G
authors.lastname: Zhu
authors.affiliation: Departments of Chemistry, and Physiology and Functional Genomics, Center for Research at the Bio/Nano Interface, Shands Cancer Center, UF Genetics Institute and McKnight Brain Institute, University of Florida, Gainesville, Florida, United States of America.
authors.forename: Xilin
authors.initials: X
authors.lastname: Xiao
authors.affiliation: Department of Pathology, Immunology and Laboratory Medicine, College of Medicine, University of Florida, Gainesville, Florida, United States of America.
authors.forename: William
authors.initials: W
authors.lastname: Puszyk
authors.affiliation: Departments of Chemistry, and Physiology and Functional Genomics, Center for Research at the Bio/Nano Interface, Shands Cancer Center, UF Genetics Institute and McKnight Brain Institute, University of Florida, Gainesville, Florida, United States of America.
authors.forename: Kwame
authors.initials: K
authors.lastname: Sefah
authors.affiliation: Department of Pathology, Immunology and Laboratory Medicine, College of Medicine, University of Florida, Gainesville, Florida, United States of America.
authors.forename: Qunfeng
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Departments of Chemistry, and Physiology and Functional Genomics, Center for Research at the Bio/Nano Interface, Shands Cancer Center, UF Genetics Institute and McKnight Brain Institute, University of Florida, Gainesville, Florida, United States of America; Molecular Sciences and Biomedicine Laboratory, State Key Laboratory for Chemo/Biosensing and Chemometrics, College of Biology and College of Chemistry and Chemical Engineering, Hunan University, Changsha, China.
authors.forename: Weihong
authors.initials: W
authors.lastname: Tan
authors.affiliation: Department of Pathology, Immunology and Laboratory Medicine, College of Medicine, University of Florida, Gainesville, Florida, United States of America.
authors.forename: Chen
authors.initials: C
authors.lastname: Liu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D052157:Aptamers, Nucleotide; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004317:Doxorubicin / Q000008:administration & dosage* / Q000494:pharmacology; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy*; D051379:Mice; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage* / Q000494:pharmacology; D023041:Xenograft Model Antitumor Assays
chemical_list: C513936:AGRO 100; D000970:Antineoplastic Agents; D052157:Aptamers, Nucleotide; D009838:Oligodeoxyribonucleotides; D004317:Doxorubicin