A tumor-targeting strategy based on covalent aptamer-carborane conjugates

The development of tumor-targeting agents is of great significance for cancer therapy. Despite the promising potential of Boron Neutron Capture Therapy (BNCT), efficient and selective accumulation of boron-10 agents in cancer cells remains challenging. Conjugation of carborane with tumor-targeting ligands provides an alternative strategy for selective accumulation in the vicinity of cancer cells. In this study, we designed and synthesized aptamer-carborane derivatives, named AS1411-CB conjugates, via covalent linkage between a dodecahydro-arachno-bis(acetonitrile)decaborane and the DNA aptamer AS1411. AS1411 specifically binds to nucleolin, which is frequently overexpressed on the surface of cancer cells, thus enables selective targeting. Circular dichroism analysis indicated that AS1411-CB conjugates retained the characteristic G-quadruplex conformation of AS1411. Incorporation of a 5-Carboxyfluorescein (FAM) fluorescent label on AS1411 allowed flow cytometry analysis, which demonstrated significantly higher association of AS1411-CB conjugates with MCF-7 breast cancer cells compared with MCF-10 A normal mammary epithelial cells. Confocal microscopy further confirmed preferential localization of AS1411-CB conjugates on the surface of MCF-7 cells, consistent with nucleolin-mediated targeting. These results demonstrated that AS1411-CB conjugates preserved the targeting capability of AS1411 and highlighted its potential as a boron delivery platform for tumor-targeting applications.