Laboratory of Molecular Imaging and Nanomedicine (LOMIN), National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH), Bethesda, Maryland 20892, USA.
Nano Lett. 2011 Feb 9;11(2):814-9. doi: 10.1021/nl104141g. Epub 2011 Jan 6.
Nanomaterials provide large surface areas, relativeto their volumes, on which to load functions. One challenge, however, has been to achieve precise control in loading multiple functionalities. Traditional bioconjugation techniques, which randomly target the surface functional groups of nanomaterials, have been found increasingly inadequate for such control, which is a drawback that may substantially slow down or prohibit the translational efforts. In the current study, we evaluated ferritin nanocages as candidate nanoplatforms for multifunctional loading. Ferritin nanocages can be either genetically or chemically modified to impart functionalities to their surfaces, and metal cations can be encapsulated in their interiors by association with metal binding sites. Moreover, different types of ferritin nanocages can be disassembled under acidic condition and reassembled at pH of 7.4, providing a facile way to achieve function hybridization. We were able to use combinations of these unique properties to produce a number of multifunctional ferritin nanostructures with precise control of their composition. We then studied these nanoparticles, both in vitro and in vivo, to evaluate their potential suitability as multimodality imaging probes. A good tumor targeting profile was observed, which was attributable to both the enhanced permeability and retention (EPR) effect and biovector mediated targeting. This, in combination with the generalizability of the function loading techniques, promises ferritin particles as a powerful nanoplatfom in the era of nanomedicine.
纳米材料相对于其体积提供了较大的表面积,可用于加载功能。然而,一个挑战是如何实现对多种功能的精确控制。传统的生物共轭技术,随机靶向纳米材料的表面功能基团,已经发现越来越不能满足这种控制,这是一个缺点,可能会大大减缓或阻止转化的努力。在本研究中,我们评估了铁蛋白纳米笼作为多功能加载的候选纳米平台。铁蛋白纳米笼可以通过基因或化学修饰在其表面赋予功能,并且金属阳离子可以通过与金属结合位点的结合被包裹在其内部。此外,不同类型的铁蛋白纳米笼可以在酸性条件下解体,并在 pH 值为 7.4 时重新组装,为实现功能杂交提供了一种简便的方法。我们能够利用这些独特性质的组合来生产多种具有精确组成控制的多功能铁蛋白纳米结构。然后,我们在体外和体内研究了这些纳米粒子,以评估它们作为多模式成像探针的潜在适用性。观察到良好的肿瘤靶向特征,这归因于增强的通透性和保留(EPR)效应和生物载体介导的靶向。这与功能加载技术的通用性相结合,有望使铁蛋白颗粒成为纳米医学时代的强大纳米平台。
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