Abstract B97: AS1411-Doxorubicin adduct for targeted liver cancer therapy.

Abstract

Abstract Background: Aptamer-drug conjugates are promising to be applied to targeted cancer therapy, in which anticancer drugs were selectively delivered into cognate cancerous cells, but not to healthy tissues, in order to reduce side effects and enhance therapeutic efficacy. Methodology/Principal Findings: In this study, the technology of drug-DNA adduct (DDA) was utilized to prepare drug-aptamer conjugates. Particularly, an anticancer drug, Doxorubicin (Dox), was conjugated with AS1411, a DNA aptamer which specifically recognizes human hepatocellular carcinoma Huh7 cells. The technology enabled a simple and high-payload conjugation of drugs onto aptamers. The resultant AS1411-Dox adduct maintained selectively recognition ability to target liver cancer cells with strong binding affinity (demonstrated by flow cytometry), was able to selectively deliver the conjugated Dox into target cancer cells (observed with confocal microscopy), and exhibited selective and potent cytotoxicity in target liver cancer cells (evaluated by MTS cell viability assay). More importantly, as the first of its kind, AS1411-Dox adduct demonstrated selectively antitumor therapeutic efficacy of this drug-aptamer conjugation technology in a mouse model. The ability of drug-aptamer adducts to deliver anticancer drugs into target cancer cells, while inhibiting nonspecific drug uptake in nontarget cells, enables this technology promising to be implemented in targeted cancer therapy. Conclusions/Significance: Given the demonstrated ability of targeted liver cancer therapy combined with the aforementioned advantageous features as a simple preparation, the high drug payload capacity, and the wide applicability, this novel drug-DNA adduct technology is anticipated for wide implications for targeted cancer therapy. Citation Information: Mol Cancer Ther 2013;12(11 Suppl):B97. Citation Format: Thu Le Trinh, Guizhi Zhu, Xilin Xiao, Xiaokui Zhang, Kwame Sefah, Weihong Tan, Chen Liu. AS1411-Doxorubicin adduct for targeted liver cancer therapy. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr B97.