Wang Yumei, Ke Jia, Guo Xianmou, Gou Kaijun, Sang Zhentao, Wang Yanbu, Bian Yan, Li Sanming, Li Heran
Department of Pharmaceutics, Shenyang Pharmaceutical University, Shenyang 110016, China.
School of Pharmacy, China Medical University, Shenyang 110122, China.
Acta Pharm Sin B. 2022 Mar;12(3):1432-1446. doi: 10.1016/j.apsb.2021.08.014. Epub 2021 Aug 18.
In the microscale, bacteria with helical body shapes have been reported to yield advantages in many bio-processes. In the human society, there are also wisdoms in knowing how to recognize and make use of helical shapes with multi-functionality. Herein, we designed atypical chiral mesoporous silica nano-screws (CMSWs) with ideal topological structures (, small section area, relative rough surface, screw-like body with three-dimension chirality) and demonstrated that CMSWs displayed enhanced bio-adhesion, mucus-penetration and cellular uptake (contributed by the macropinocytosis and caveolae-mediated endocytosis pathways) abilities compared to the chiral mesoporous silica nanospheres (CMSSs) and chiral mesoporous silica nanorods (CMSRs), achieving extended retention duration in the gastrointestinal (GI) tract and superior adsorption in the blood circulation (up to 2.61- and 5.65-times in AUC). After doxorubicin (DOX) loading into CMSs, DOX@CMSWs exhibited controlled drug release manners with pH responsiveness . Orally administered DOX@CMSWs could efficiently overcome the intestinal epithelium barrier (IEB), and resulted in satisfactory oral bioavailability of DOX (up to 348%). CMSWs were also proved to exhibit good biocompatibility and unique biodegradability. These findings displayed superior ability of CMSWs in crossing IEB through multiple topological mechanisms and would provide useful information on the rational design of nano-drug delivery systems.
在微观尺度上，据报道具有螺旋体形状的细菌在许多生物过程中具有优势。在人类社会中，对于如何识别和利用具有多功能的螺旋形状也有智慧。在此，我们设计了具有理想拓扑结构（小截面面积、相对粗糙的表面、具有三维手性的螺旋状主体）的非典型手性介孔二氧化硅纳米螺旋（CMSWs），并证明与手性介孔二氧化硅纳米球（CMSSs）和手性介孔二氧化硅纳米棒（CMSRs）相比，CMSWs表现出增强的生物粘附、黏液穿透和细胞摄取（由巨胞饮作用和小窝介导的内吞途径促成）能力，在胃肠道（GI）中实现了延长的保留时间，并在血液循环中具有优异的吸附性能（AUC高达2.61倍和5.65倍）。将阿霉素（DOX）负载到CMSWs中后，DOX@CMSWs表现出具有pH响应性的可控药物释放方式。口服DOX@CMSWs能够有效克服肠道上皮屏障（IEB），并使DOX具有令人满意的口服生物利用度（高达348%）。还证明CMSWs具有良好的生物相容性和独特的生物降解性。这些发现显示了CMSWs通过多种拓扑机制穿越IEB的卓越能力，并将为纳米药物递送系统的合理设计提供有用信息。
