Anti-nucleolin aptamer-guided anticancer activity of AS1411-Chalcone conjugate in breast cancer

초록

The DNA aptamer AS1411 is a 26-nucleotide, guanine-rich oligonucleotide with high specificity for nucleolin-a multifunctional protein overexpressed on the surface of many cancer cells and involved in key processes such as proliferation and apoptosis. By selectively binding nucleolin, AS1411 serves as an ideal targeting ligand for delivering therapeutic agents. Chalcone, a naturally occurring flavonoid with documented anticancer activity, induces apoptosis and inhibits tumor growth; however, its clinical utility is limited by nonspecific cytotoxicity. In this study, we synthesized a novel aptamer-drug conjugate by covalently linking chalcone to AS1411, thereby leveraging the aptamer's targeting ability to enhance drug delivery specifically to cancer cells. Comprehensive characterization using UV-visible spectroscopy, FTIR, and zeta potential analysis confirmed successful conjugation and favorable physicochemical properties. In vitro assays revealed that the AS1411-chalcone conjugate significantly improved anticancer efficacy in MCF-7 breast cancer cells by reducing the IC50 from 96.6 mu g/mL (free chalcone) to 74.4 mu g/mL and by achieving a 50 % reduction in colony formation. Moreover, the conjugate exhibited reduced cytotoxicity toward normal HDF cells and induced cell cycle arrest and apoptotic cell death selectively in cancer cells. These findings highlight the potential of AS1411-mediated chalcone delivery as a targeted therapeutic strategy that enhances drug potency while minimizing off-target effects.

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