California NanoSystems Institute and Department of Chemistry and Biochemistry, University of California, Los Angeles, 607 Charles E. Young Drive East, Los Angeles, California 90095, USA.
J Am Chem Soc. 2010 Sep 22;132(37):13016-25. doi: 10.1021/ja105371u.
The development of drug delivery systems for the targeted and on-demand release of pharmaceutical products has risen rapidly to become a contemporary challenge in the field of nanobiotechnology. Biocompatible mechanized phosphonate-clothed silica nanoparticles have been designed and fabricated in which the supramolecular machinery, which covers the surfaces of the nanoparticles, behaves like nanopistons, releasing encapsulated guest molecules in a controlled fashion under acidic conditions. The mechanized nanoparticles consist of a monolayer of β-cyclodextrin (β-CD) rings positioned selectively around the orifices of the nanopores of the mesoporous nanoparticles. A rhodamine B/benzidine conjugate was prepared for use as the nanopistons for movement in and out of the cylindrical cavities provided by the β-CD rings on the surfaces of the nanoparticles. Luminescence experiments indicated that the mechanized nanoparticles were able to store small cargo molecules (e.g., 2,6-naphthalenedisulfonic acid disodium) within their nanopores at neutral pH and then release them by passage through the cavities of the β-CD rings as soon as the pH was lowered to ∼5. In further investigations, the phosphonate-covered silica nanoparticles were functionalized selectively with the β-CD rings, but on this occasion, the seven linkers attaching the rings to the orifices surrounding the nanopores contained cleavable imine double bonds. The β-CD rings on the surface of the nanoparticles served as gates for the storage of large cargo molecules (e.g., rhodamine B) inside the nanopores of the nanoparticles under neutral conditions. Since imine bonds can be hydrolyzed under acidic conditions, the β-CD rings could be severed from the surface of the nanoparticles when the pH was decreased to 6, releasing the large cargo molecules. The results described here present a significant step toward the development of pH-responsive nanoparticle-based dual drug delivery vehicles that are potentially capable of being interfaced with biological systems.
用于药物靶向和按需释放的药物输送系统的发展迅速成为纳米生物技术领域的当代挑战。已经设计和制造了生物相容的机械化膦酸酯涂覆的硅纳米粒子，其中覆盖纳米粒子表面的超分子机械装置的行为类似于纳米活塞，在酸性条件下以受控方式释放封装的客体分子。机械化纳米粒子由选择性地位于介孔纳米粒子的纳米孔的孔口周围的单层β-环糊精（β-CD）环组成。制备了罗丹明 B/联苯胺缀合物用作纳米活塞，用于在纳米粒子表面的β-CD 环提供的圆柱形腔体内进出运动。发光实验表明，机械化纳米粒子能够在中性 pH 下将小货物分子（例如，2,6-萘二磺酸二钠盐）储存在其纳米孔内，然后一旦 pH 降低至约 5，即可通过β-CD 环的腔释放它们。在进一步的研究中，膦酸酯覆盖的硅纳米粒子被选择性地官能化带有β-CD 环，但在这种情况下，将环连接到围绕纳米孔的孔口的七个接头包含可裂解的亚胺双键。纳米粒子表面上的β-CD 环充当纳米孔内大货物分子（例如，罗丹明 B）在中性条件下存储的门。由于亚胺键可以在酸性条件下水解，因此当 pH 降低至 6 时，可以将β-CD 环从纳米粒子表面切断，从而释放出大的货物分子。这里描述的结果是朝着开发基于 pH 响应的纳米粒子的双重药物输送载体迈出的重要一步，该载体有可能与生物系统接口。
