Cancer metastatic spread is life-threatening and caused by circulating tumor cells (CTCs) that are very difficult to precisely capture in vivo. Here we show that two aptamer rings targeting different CTC biomarker epitopes conjugated on dendrimers capture CTCs with enhanced precision even in the presence of 108 interfering cells, or blood cells, and in mice or patient samples when compared with their single aptamer counterparts. The aptamer-conjugate inhibited in vivo metastasis and demonstrated enhanced biostability by resisting biodegradation caused by the endogenous nucleases. The capture arms of the aptamer conjugates could simultaneously and specifically seize two biomarkers (EpCAM and Her2). The double seizure resulted in significant cell-cycle arrest, apoptosis, and growth inhibition of the captured CTCs. The aptamer-conjugate highly penetrated and accumulated in mouse tumors. This study provides the first conceptual evidence that two aptamer rings, inexpensive but bioequivalent to their antibodies, can be biocompatibly conjugated to specifically capture and down-regulate CTCs in vivo with the enhanced biostability.

Ursolic acid and doxorubicin co-assembled into nanoparticles were modified with an aptamer for enhanced anti-tumor effects.

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