Department of Otolaryngology, Medical University of Innsbruck, Anichstr. 35, A-6020 Innsbruck, Austria.
Int J Pharm. 2010 May 10;390(2):214-24. doi: 10.1016/j.ijpharm.2010.02.003. Epub 2010 Feb 11.
Cell specific targeting is an emerging field in nanomedicine. Homing of the multifunctional nanoparticles (MFNPs) is achieved by the conjugation of targeting moieties on the nanoparticle surface. The inner ear is an attractive target for new drug delivery strategies as it is hard to access and hearing loss is a significant worldwide problem. In this work we investigated the utility of a Nerve Growth Factor-derived peptide (hNgf_EE) functionalized nanoparticles (NPs) to target cells of the inner ear. These functionalized NPs were introduced to organotypic explant cultures of the mouse inner ear and to PC-12 rat pheochromocytoma cells. The NPs did not show any signs of toxicity. Specific targeting and higher binding affinity to spiral ganglion neurons, Schwann cells and nerve fibers of the explant cultures were achieved through ligand mediated multivalent binding to tyrosine kinase receptors and to p75 neurotrophin receptors. Unspecific uptake of NPs was investigated using NPs conjugated with scrambled hNgf_EE peptide. Our results indicate a selective cochlear cell targeting by MFNPs, which may be a potential tool for cell specific drug and gene delivery to the inner ear.
细胞特异性靶向是纳米医学领域的一个新兴领域。通过在纳米粒子表面缀合靶向部分,实现多功能纳米粒子(MFNPs)的归巢。内耳是新药物输送策略的一个有吸引力的靶标,因为它很难接近,而且听力损失是一个全球性的重大问题。在这项工作中,我们研究了神经营养因子衍生肽(hNgf_EE)功能化纳米粒子(NPs)靶向内耳细胞的应用。这些功能化 NPs 被引入到小鼠内耳的器官型外植体培养物和 PC-12 大鼠嗜铬细胞瘤细胞中。这些 NPs 没有表现出任何毒性迹象。通过配体介导的多价结合到酪氨酸激酶受体和 p75 神经营养素受体,实现了对螺旋神经节神经元、施万细胞和外植体培养物的神经纤维的特异性靶向和更高的结合亲和力。通过与 scrambled hNgf_EE 肽缀合的 NPs 研究了 NPs 的非特异性摄取。我们的结果表明,MFNPs 可以选择性地靶向耳蜗细胞,这可能是内耳细胞特异性药物和基因传递的潜在工具。