A dual-targeting DNA tetrahedron nanocarrier for breast cancer cell imaging and drug delivery

Abstract

To enhance efficacy of chemotherapy and achieve real-time imaging of cancer cells, it is crucial to develop nanocarriers with targeted drug delivery capacity and fluorescence property for cancer theranostics. Herein, a dual-targeting DNA tetrahedron nanocarrier (MUC1-Td-AS1411) was constructed for breast cancer cell imaging and targeted drug delivery. This nanocarrier consisted of three components: (i) DNA tetrahedron core for multivalent conjugation of function ligands and loading doxorubicin (Dox); (ii) activatable MUC1 aptamer probe (MUC1-probe), formed by the hybridization of MUC1 aptamer sequence with fluorophore extended from one vertex and complementary sequence with quencher, for targeting and imaging MUC1 protein on cytomembrane; (iii) AS1411 aptamer, which was hybridized to the overhang on three vertexes via prolonged sequence, for binding to nucleolin. Firstly, MUC1-probe of this nanocarrier targeted MUC1 protein of MUC1-positive cells, causing a conformational reorganization of MUC1 aptamer, releasing complementary sequence with quencher and leading to fluorescence recovery. Subsequently, after internalizing into cells, AS1411 aptamer moiety of nanocarrier bound to nucleolin selectively, then the whole nanocarrier targeted nucleus and released Dox into nucleus. MUC1-positive cells and MUC1-negative cells could be differentiated by means of fluorescence imaging. Versus free Dox, Dox-loaded MUC1-Td-AS1411 showed lower cytotoxicity to MUC1-negative HL-7702 cells (P < 0.01), approximately equal lethality to sensitive MCF-7 cells (P > 0.05) whereas more effective to doxorubicin-resistant MCF-7 cells (P < 0.01). Therefore, this nanocarrier could be used as a promising candidate for cancer theranostics.