Department of Physics, Tsinghua University, Beijing 10008, China.
J Mater Chem B. 2019 Mar 28;7(12):2043-2053. doi: 10.1039/c8tb03349h. Epub 2019 Feb 22.
Nanotube materials exhibit high drug loading capacity and controlled drug release properties, providing new opportunities for drug delivery. However, the intracellular trafficking paths of 1-dimensional (1D) nanostructured materials are poorly understood compared to their spherical counterparts, impeding the broad application of 1D materials as drug carriers. Here, we report the intracellular trafficking mechanism of nontoxic and biocompatible nanomaterials called anodic alumina nanotubes (AANTs), a model for 1D materials with a geometry that can be precisely engineered. The results indicated that AANTs enter the cells mainly by caveolin endocytosis and micropinocytosis and that cells use a novel macropinocytosis-late endosomes (LEs)-lysosomes route to transport AANTs. Moreover, liposomes (marked by DsRed-Rab18) are fully involved in the classical pathway of early endosomes (EEs)/LEs developing into lysosomes. The AANTs were delivered to the cells via two pathways: slow endocytosis recycling and GLUT4 exocytosis vesicles. The AANTs also induced intracellular autophagy and then degraded via the endolysosomal pathway. Blocking endolysosomal pathways using autophagy inhibitors prevented the degradation of AANTs through lysosomes. Our results add new insights into the pathways and mechanisms of intracellular trafficking of AANTs, and suggest that intracellular trafficking and lysosomal degradation are highly interdependent and important for efficient drug delivery, and should be evaluated together for drug carrier development.
纳米管材料表现出高的药物负载能力和控制药物释放的特性，为药物传递提供了新的机会。然而，与球形纳米材料相比，一维（1D）纳米结构材料的细胞内转运途径知之甚少，这阻碍了 1D 材料作为药物载体的广泛应用。在这里，我们报告了一种叫做阳极氧化铝纳米管（AANTs）的无毒和生物相容的纳米材料的细胞内转运机制，AANTs 是一种可以精确设计的一维材料的模型。结果表明，AANTs 主要通过胞饮作用和微吞噬作用进入细胞，细胞利用一种新的巨胞饮晚期内涵体（LEs）-溶酶体途径来运输 AANTs。此外，脂质体（用 DsRed-Rab18 标记）完全参与了早期内涵体（EEs）/LEs 向溶酶体发展的经典途径。AANTs 通过两种途径被递送到细胞内：缓慢的内体再循环和 GLUT4 胞吐囊泡。AANTs 还诱导细胞内自噬，然后通过内溶酶体途径降解。用自噬抑制剂阻断内溶酶体途径可以防止 AANTs 通过溶酶体降解。我们的结果为 AANTs 的细胞内转运途径和机制提供了新的见解，并表明细胞内转运和溶酶体降解是高效药物传递的高度相互依赖和重要的，并且应该一起评估用于药物载体的开发。
