Targeted suicide gene transfections reveal promising results in nu/nu mice with aggressive neuroblastoma.

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.