Shanghai Institute of Materia Medica, Chinese Academy of Sciences , Shanghai 201203, China.
University of Chinese Academy of Sciences , NO.19A Yuquan Road, Beijing 100049, China.
Nano Lett. 2016 Nov 9;16(11):7176-7182. doi: 10.1021/acs.nanolett.6b03515. Epub 2016 Oct 7.
Mucus is a viscoelastic gel layer that typically protects exposed surfaces of the gastrointestinal (GI) tract, lung airways, and other mucosal tissues. Particles targeted to these tissues can be efficiently trapped and removed by mucus, thereby limiting the effectiveness of such drug delivery systems. In this study, we experimentally and theoretically demonstrated that cylindrical nanoparticles (NPs), such as mesoporous silica nanorods and calcium phosphate nanorods, have superior transport and trafficking capability in mucus compared with spheres of the same chemistry. The higher diffusivity of nanorods leads to deeper mucus penetration and a longer retention time in the GI tract than that of their spherical counterparts. Molecular simulations and stimulated emission of depletion (STED) microscopy revealed that this anomalous phenomenon can be attributed to the rotational dynamics of the NPs facilitated by the mucin fibers and the shear flow. These findings shed new light on the shape design of NP-based drug delivery systems targeted to mucosal and tumor sites that possess a fibrous structure/porous medium.
黏液是一种黏弹性凝胶层，通常可保护胃肠道 (GI) 道、肺部气道和其他黏膜组织的暴露表面。靶向这些组织的颗粒可被黏液有效捕获和清除，从而限制了此类药物输送系统的有效性。在这项研究中，我们通过实验和理论证明，与具有相同化学性质的球体相比，圆柱形纳米颗粒 (NPs)，如介孔硅纳米棒和磷酸钙纳米棒，在黏液中有更好的传输和迁移能力。纳米棒的更高扩散性导致其在 GI 道中的穿透更深，并在其中的停留时间更长。分子模拟和受激发射损耗 (STED) 显微镜显示，这种异常现象可归因于 NPs 的旋转动力学，这是由黏蛋白纤维和切变流促成的。这些发现为基于 NP 的药物输送系统的形状设计提供了新的思路，这些系统针对具有纤维结构/多孔介质的黏膜和肿瘤部位。
