Neuroblastoma represents the third most common malign neoplasm occurring in children and the most common in newborn. Although mortality in childhood cancer declined in the last decade, high-risk patients have poor prospects, due to the aggressiveness of the cancer. In the recent past, we underlined the potential of sapofectosid as novel and efficient transfection enhancer, demonstrating non-toxic gene delivery, but its value in tumor therapies has yet to be elucidated. A suicide gene, coding for saporin, a ribosome-inactivating protein type I, was incorporated into targeted, peptide-based nanoplexes. The nanoplexes were characterized for their size, zeta potential and appearance by electron microscopy. Gene delivery was observed via confocal imaging. In vitro transfections were conducted to monitor the real-time cell viability. After initial tolerability studies, NMRI nu/nu-mice bearing tumors from Neuro-2A-Luc-cells (murine neuroblastoma cells, transduced with a luciferase gene), were treated with targeted nanoplexes (30 μg saporin-DNA i.v./treatment) and sapofectosid (30 μg s.c. treatment). The treatment was compared to a vehicle (PBS) control and treatment without sapofectosid in terms of body weight, tumor growth and integrated density of tumor luminescence. The study revealed an anti-tumoral effect of the sapofectosid mediated gene therapy in the Neuro-2A-tumor model. The treatments were well tolerated by the animals indicating the applicability of this approach. With these results, we were able to proof the efficacy of a therapy, consisting of targeted suicide gene nanoplexes and sapofectosid, a novel and potent transfection enhancer. This study points out the enormous value for future targeted cancer and gene therapies.

神经母细胞瘤是儿童中第三常见的恶性肿瘤，也是新生儿中最常见的肿瘤。尽管儿童癌症的死亡率在过去十年中有所下降，但由于癌症的侵袭性，高危患者的前景不佳。最近，我们强调了 sapofectosid 作为新型高效转染增强剂的潜力，证明了无毒的基因传递，但其在肿瘤治疗中的价值尚未阐明。编码皂草素（I 型核糖体失活蛋白）的自杀基因被整合到基于肽的靶向纳米复合物中。通过电子显微镜对纳米复合物的尺寸、zeta 电位和外观进行了表征。通过共焦成像观察基因传递。进行体外转染以监测实时细胞活力。经过初步耐受性研究后，使用靶向纳米复合物（30 μg 皂素-DNA 静脉注射/治疗）和 sapofectosid 治疗带有来自 Neuro-2A-Luc 细胞（鼠神经母细胞瘤细胞，用荧光素酶基因转导）肿瘤的 NMRI nu/nu-小鼠(30μg皮下治疗)。将治疗与媒介物（PBS）对照和不含sapofectosid的治疗在体重、肿瘤生长和肿瘤发光的积分密度方面进行比较。该研究揭示了 sapofectosid 介导的基因治疗在 Neuro-2A 肿瘤模型中的抗肿瘤作用。动物对治疗的耐受性良好，表明该方法的适用性。通过这些结果，我们能够证明由靶向自杀基因纳米复合物和 sapofectosid（一种新型有效的转染增强剂）组成的疗法的功效。这项研究指出了未来靶向癌症和基因疗法的巨大价值。