Porciani David, Tedeschi Lorena, Marchetti Laura, Citti Lorenzo, Piazza Vincenzo, Beltram Fabio, Signore Giovanni
1] NEST, Scuola Normale Superiore and Istituto Nanoscienze-CNR, Pisa, Italy [2] Center for Nanotechnology Innovation@NEST, Istituto Italiano di Tecnologia, Pisa, Italy.
CNR, Institute of Clinical Physiology, Pisa, Italy.
Mol Ther Nucleic Acids. 2015 Apr 28;4(4):e235. doi: 10.1038/mtna.2015.9.
Aptamers able to bind efficiently cell-surface receptors differentially expressed in tumor and in healthy cells are emerging as powerful tools to perform targeted anticancer therapy. Here, we present a novel oligonucleotide chimera, composed by an RNA aptamer and a DNA decoy. Our assembly is able to (i) target tumor cells via an antitransferrin receptor RNA aptamer and (ii) perform selective codelivery of a chemotherapeutic drug (Doxorubicin) and of an inhibitor of a cell-survival factor, the nuclear factor κB decoy oligonucleotide. Both payloads are released under conditions found in endolysosomal compartments (low pH and reductive environment). Targeting and cytotoxicity of the oligonucleotidic chimera were assessed by confocal microscopy, cell viability, and Western blot analysis. These data indicated that the nuclear factor κB decoy does inhibit nuclear factor κB activity and ultimately leads to an increased therapeutic efficacy of Doxorubicin selectively in tumor cells.
能够有效结合在肿瘤细胞和健康细胞中差异表达的细胞表面受体的适体，正成为进行靶向抗癌治疗的有力工具。在此，我们展示了一种新型寡核苷酸嵌合体，它由一个RNA适体和一个DNA诱饵组成。我们的组装体能够（i）通过抗转铁蛋白受体RNA适体靶向肿瘤细胞，以及（ii）对化疗药物（阿霉素）和一种细胞存活因子抑制剂——核因子κB诱饵寡核苷酸进行选择性共递送。两种负载物都在内溶酶体区室（低pH和还原环境）中发现的条件下释放。通过共聚焦显微镜、细胞活力和蛋白质免疫印迹分析评估了寡核苷酸嵌合体的靶向性和细胞毒性。这些数据表明，核因子κB诱饵确实抑制核因子κB活性，并最终导致阿霉素在肿瘤细胞中的治疗效果选择性增加。
