Borroni Ester, Miola Marta, Ferraris Sara, Ricci Giulia, Žužek Rožman Kristina, Kostevšek Nina, Catizone Angela, Rimondini Lia, Prat Maria, Verné Enrica, Follenzi Antonia
Dept. of Health Sciences, Università del Piemonte Orientale "A. Avogadro", Novara, Italy.
Dept. of Applied Science and Technology, Politecnico di Torino, Torino, Italy.
Acta Biomater. 2017 Sep 1;59:303-316. doi: 10.1016/j.actbio.2017.07.007. Epub 2017 Jul 5.
Nanomaterials conjugated or complexed with biological moieties such as antibodies, polymers or peptides appear to be suitable not only for drug delivery but also for specific cancer treatment. Here, biocompatible iron oxide magnetic nanoparticles (MNPs) with or without a silica shell coupled with lentiviral vectors (LVs) are proposed as a combined therapeutic approach to specifically target gene expression in a cancer mouse model. Initially, four different MNPs were synthesized and their physical properties were characterized to establish and discriminate their behaviors. MNPs and LVs strictly interacted and transduced cells in vitro as well as in vivo, with no toxicity or inflammatory responses. By injecting LV-MNPs complexes intravenously, green fluorescent protein (GFP) resulted in a sustained long-term expression. Furthermore, by applying a magnetic field on the abdomen of intravenous injected mice, GFP positive cells increased in livers and spleens. In liver, LV-MNPs were able to target both hepatocytes and non-parenchymal cells, while in a mouse model with a grafted tumor, intra-tumor LV-MNPs injection and magnetic plaque application next to the tumor demonstrated the efficient uptake of LV-MNPs complexes with high number of transduced cells and iron accumulation in the tumor site. More important, LV-MNPs with the application of the magnetic plaque spread in all the tumor parenchyma and dissemination through the body was prevented confirming the efficient uptake of LV-MNPs complexes in the tumor. Thus, these LV-MNPs complexes could be used as multifunctional and efficient tools to selectively induce transgene expression in solid tumor for therapeutic purposes.
Our study describes a novel approach of combining magnetic properties of nanomaterials with gene therapy. Magnetic nanoparticles (MNPs) coated with or without a silica shell coupled with lentiviral vectors (LVs) were used as vehicle to target biological active molecules in a mouse cancer model. After in situ injection, the presence of MNP under the magnetic field improve the vector distribution in the tumor mass and after systemic administration, the application of the magnetic field favor targeting of specific organs for LV transduction and specifically can direct LV in specific cells (or avoiding them). Thus, our findings suggest that LV-MNPs complexes could be used as multifunctional and efficient tools to selectively induce transgene expression in solid tumor for therapeutic purposes.
与生物部分（如抗体、聚合物或肽）共轭或复合的纳米材料似乎不仅适用于药物递送，还适用于特定的癌症治疗。在此，提出将具有或不具有二氧化硅壳的生物相容性氧化铁磁性纳米颗粒（MNP）与慢病毒载体（LV）结合，作为在癌症小鼠模型中特异性靶向基因表达的联合治疗方法。最初，合成了四种不同的MNP，并对其物理性质进行了表征，以确定和区分它们的行为。MNP和LV在体外和体内都能严格相互作用并转导细胞，且无毒性或炎症反应。通过静脉注射LV-MNP复合物，绿色荧光蛋白（GFP）实现了持续的长期表达。此外，对静脉注射小鼠的腹部施加磁场后，肝脏和脾脏中的GFP阳性细胞增加。在肝脏中，LV-MNP能够靶向肝细胞和非实质细胞，而在移植肿瘤的小鼠模型中，肿瘤内注射LV-MNP并在肿瘤旁施加磁斑，证明LV-MNP复合物能被有效摄取，肿瘤部位有大量转导细胞和铁积累。更重要的是，施加磁斑的LV-MNP在所有肿瘤实质中扩散，并防止了其在体内的扩散，证实了LV-MNP复合物在肿瘤中的有效摄取。因此，这些LV-MNP复合物可作为多功能高效工具，用于在实体瘤中选择性诱导转基因表达以达到治疗目的。
我们的研究描述了一种将纳米材料的磁性与基因治疗相结合的新方法。涂有或未涂有二氧化硅壳并与慢病毒载体（LV）结合的磁性纳米颗粒（MNP）被用作载体，以在小鼠癌症模型中靶向生物活性分子。原位注射后，磁场下MNP的存在改善了载体在肿瘤块中的分布，全身给药后，磁场的应用有利于LV转导靶向特定器官，并且特别能将LV导向特定细胞（或避开它们）。因此，我们的研究结果表明，LV-MNP复合物可作为多功能高效工具，用于在实体瘤中选择性诱导转基因表达以达到治疗目的。
