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.

为了增强化学疗法的疗效并实现癌细胞的实时成像，开发具有靶向药物传递能力和荧光特性的纳米载体对于癌症治疗学家至关重要。本文中，构建了双重靶向DNA四面体纳米载体（MUC1-Td-AS1411），用于乳腺癌细胞成像和靶向药物递送。该纳米载体由三部分组成：（i）DNA四面体核心，用于功能配体的多价结合和负载阿霉素（Dox）；（ii）可活化的MUC1适体探针（MUC1-探针），通过将MUC1适体序列与从一个顶点延伸的荧光团和互补序列与淬灭剂杂交形成，用于在细胞膜上靶向和成像MUC1蛋白; （iii）AS1411适体，通过延长的序列与三个顶点的突出端杂交，与核仁素结合。首先，这种纳米载体的MUC1探针靶向MUC1阳性细胞的MUC1蛋白，引起MUC1适体的构象重组，释放具有猝灭剂的互补序列并导致荧光恢复。随后，内化进入细胞后，纳米载体的AS1411适体部分选择性地与核仁素结合，然后整个纳米载体靶向核并释放Dox进入核。MUC1阳性细胞和MUC1阴性细胞可以通过荧光成像进行区分。与不含Dox的Dox相比，载有Dox的MUC1-Td-AS1411对MUC1阴性的HL-7702细胞具有较低的细胞毒性（P <0.01），与对敏感的MCF-7细胞的致死率大致相同（P> 0.05），而对阿霉素抗性更有效MCF-7细胞（P <0.01）。所以，