Marcus Michal, Smith Alexandra, Maswadeh Ahmad, Shemesh Ziv, Zak Idan, Motiei Menachem, Schori Hadas, Margel Shlomo, Sharoni Amos, Shefi Orit
Faculty of Engineering, Bar Ilan University, Ramat Gan 5290002, Israel.
Bar Ilan Institute of Nanotechnologies and Advanced Materials, Ramat Gan 5290002, Israel.
Nanomaterials (Basel). 2018 Sep 10;8(9):707. doi: 10.3390/nano8090707.
Growth factors play an important role in nerve regeneration and repair. An attractive drug delivery strategy, termed "magnetic targeting", aims to enhance therapeutic efficiency by directing magnetic drug carriers specifically to selected cell populations that are suitable for the nervous tissues. Here, we covalently conjugated nerve growth factor to iron oxide nanoparticles (NGF-MNPs) and used controlled magnetic fields to deliver the NGF⁻MNP complexes to target sites. In order to actuate the magnetic fields a modular magnetic device was designed and fabricated. PC12 cells that were plated homogenously in culture were differentiated selectively only in targeted sites out of the entire dish, restricted to areas above the magnetic "hot spots". To examine the ability to guide the NGF-MNPs towards specific targets in vivo, we examined two model systems. First, we injected and directed magnetic carriers within the sciatic nerve. Second, we injected the MNPs intravenously and showed a significant accumulation of MNPs in mouse retina while using an external magnet that was placed next to one of the eyes. We propose a novel approach to deliver drugs selectively to injured sites, thus, to promote an effective repair with minimal systemic side effects, overcoming current challenges in regenerative therapeutics.
生长因子在神经再生和修复中发挥着重要作用。一种颇具吸引力的药物递送策略,称为“磁靶向”,旨在通过将磁性药物载体特异性地导向适合神经组织的选定细胞群体来提高治疗效率。在此,我们将神经生长因子共价偶联到氧化铁纳米颗粒(NGF-MNPs)上,并利用可控磁场将NGF-MNP复合物递送至靶位点。为了驱动磁场,设计并制造了一种模块化磁性装置。均匀接种在培养皿中的PC12细胞仅在整个培养皿中的靶位点选择性分化,这些靶位点局限于磁性“热点”上方的区域。为了研究在体内将NGF-MNPs导向特定靶标的能力,我们研究了两个模型系统。首先,我们在坐骨神经内注射并引导磁性载体。其次,我们静脉注射MNPs,并在使用置于一只眼睛旁边的外部磁体时,显示MNPs在小鼠视网膜中有显著积累。我们提出了一种将药物选择性递送至损伤部位的新方法,从而以最小的全身副作用促进有效修复,克服再生治疗中的当前挑战。