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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.
AuthorsThu Le Trinh, Guizhi Zhu, Xilin Xiao, William Puszyk, Kwame Sefah, Qunfeng Wu, Weihong Tan, Chen Liu
JournalPloS one (PLoS One) Vol. 10 Issue 11 Pg. e0136673 ( 2015) ISSN: 1932-6203 [Electronic] United States
PMID26523833 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
Chemical References
  • AGRO 100
  • Antineoplastic Agents
  • Aptamers, Nucleotide
  • Oligodeoxyribonucleotides
  • Doxorubicin
Topics
  • Animals
  • Antineoplastic Agents (administration & dosage, pharmacology)
  • Aptamers, Nucleotide
  • Cell Cycle (drug effects)
  • Cell Line, Tumor
  • Cell Proliferation (drug effects)
  • Doxorubicin (administration & dosage, pharmacology)
  • Humans
  • Liver Neoplasms (drug therapy)
  • Mice
  • Oligodeoxyribonucleotides (administration & dosage, pharmacology)
  • Xenograft Model Antitumor Assays

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