Original articles
Yumei Wang, Jia Ke, Xianmou Guo, Kaijun Gou, Zhentao Sang, Yanbu Wang, Yan Bian, Sanming Li, Heran Li. Chiral mesoporous silica nano-screws as an efficient biomimetic oral drug delivery platform through multiple topological mechanisms[J]. Acta Pharmaceutica Sinica B, 2022, 12(3): 1432-1446

Chiral mesoporous silica nano-screws as an efficient biomimetic oral drug delivery platform through multiple topological mechanisms
Yumei Wanga, Jia Kea, Xianmou Guoa, Kaijun Goua, Zhentao Sangb, Yanbu Wanga,b, Yan Bianb, Sanming Lia, Heran Lib
a. Department of Pharmaceutics, Shenyang Pharmaceutical University, Shenyang 110016, China;
b. School of Pharmacy, China Medical University, Shenyang 110122, China
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 (e.g., 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 in vitro. 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.
Key words:    Chiral mesoporous silica    Nano-screw    Morphology    Geometric topological structure    Intestinal epithelium barrier    Oral adsorption   
Received: 2021-06-07     Revised: 2021-07-08
DOI: 10.1016/j.apsb.2021.08.014
Funds: This article was funded by the National Natural Science Foundation of China (Nos. 81773672 and 81903550).
Corresponding author: Sanming Li,E-mai:li_sanming@126.com;Heran Li,E-mai:liheranmm@163.com     Email:li_sanming@126.com;liheranmm@163.com
Author description:
PDF(KB) Free
Yumei Wang
Jia Ke
Xianmou Guo
Kaijun Gou
Zhentao Sang
Yanbu Wang
Yan Bian
Sanming Li
Heran Li

[1] Hristov D, McCartney F, Beirne J, Mahon E, Reid S, Bhattacharjee S, et al. Silica-coated nanoparticles with a core of zinc, L-arginine, and a peptide designed for oral delivery. Acs Appl Mater Inter 2020; 12: 1257-1269
[2] Wu X, Qiu H, Che S. Controlling the pitch length of helical mesoporous silica (HMS). Micropor Mesopor Mat 2009; 120: 294-303
[3] Jin H, Liu Z, Ohsuna T, Terasaki O, Inoue Y, Sakamoto K, et al. Control of morphology and helicity of chiral mesoporous silica. Adv Mater 2006; 18: 593-596
[4] Choonara BF, Choonara YE, Kumar P, Bijukumar D, du Toit LC, Pillay V. A review of advanced oral drug delivery technologies facilitating the protection and absorption of protein and peptide molecules. Biotechnol Adv 2014; 32: 1269-1282
[5] Yun Y, Cho YW, Park K. Nanoparticles for oral delivery: targeted nanoparticles with peptidic ligands for oral protein delivery. Adv Drug Deliver Rev 2013; 65: 822-832
[6] Bao C, Liu B, Li B, Chai J, Zhang L, Jiao L, et al. Enhanced transport of shape and rigidity-tuned alpha-lactalbumin nanotubes across intestinal mucus and cellular barriers. Nano Lett 2020; 20: 1352-1361
[7] Yu M, Yang Y, Zhu C, Guo S, Gan Y. Advances in the transepithelial transport of nanoparticles. Drug Discov Today 2016; 21: 1155-1161
[8] Chen MC, Sonaje K, Chen KJ. A review of the prospects for polymeric nanoparticle platforms in oral insulin delivery. Biomaterials 2011; 32: 9826-9838
[9] Lane LA, Qian X, Smith AM, Nie S. Physical chemistry of nanomedicine: understanding the complex behaviors of nanoparticles in vivo. Annu Rev Phys Chem 2015; 66: 521-547
[10] Yu M, Wang J, Yang Y, Zhu C, Su CH, Guo S, et al. Rotation-facilitated rapid transport of nanorods in mucosal tissues. Nano Lett 2016; 16: 7176-7182
[11] Shiomi D. Erratum to: Polar localization of MreB actin is inhibited by anionic phospholipids in the rod-shaped bacterium Escherichia coli. Curr Genet 2017; 63: 849
[12] Young KD. Bacterial morphology: why have different shapes?. Curr Opin Microbiol 2007; 10: 596-600
[13] Wang W, Wang P, Tang X, Elzatahry AA, Wang S, Al-Dahyan D, et al. Facile synthesis of uniform virus-like mesoporous silica nanoparticles for enhanced cellular internalization. Acs Central Sci 2017; 3: 839-846
[14] Zheng N, Li J, Xu C, Xu L, Li S, Xu L. Mesoporous silica nanorods for improved oral drug absorption. Artif Cell Nanomed B 2018; 46: 1132-1140
[15] Maira AC, Mehdi J, Henry CF, Rama B. Helical and rod-shaped bacteria swim in helical trajectories with little additional propulsion from helical shape. Sci Adv 2016; 2: e1601661
[16] Sycuro LK, Wyckoff TJ, Biboy J, Born P, Pincus Z, Vollmer W, et al. Multiple peptidoglycan modification networks modulate Helicobacter pylori's cell shape, motility, and colonization potential. Plos Pathog 2012; 8: e1002603
[17] Frirdich E, Biboy J, Adams C, Lee J, Ellermeier J, Gielda LD, et al. Peptidoglycan-modifying enzyme Pgp1 is required for helical cell shape and pathogenicity traits in Campylobacter jejuni. PLoS Pathog 2012; 8: e1002602
[18] Wu SH, Mou CY, Lin HP. 3D cubic mesoporous silica microsphere as a carrier for poorly soluble drug carvedilol. Chem Soc Rev 2013; 42: 3862-3875
[19] Hu B, Sun W, Li H, Sui H, Li S. Systematic modifications of amino acid-based organogelators for the investigation of structure-property correlations in drug delivery system. Int J Pharmaceut 2018; 547: 637-647
[20] Yokoi T, Yamataka Y, Ara Y, Sato S, Kubota Y, Tatsumi T. Synthesis of chiral mesoporous silica by using chiral anionic surfactants. Micropor Mesopor Mat 2008; 103: 20-28
[21] Li J, Xu L, Yang B. Biomimetic synthesized chiral mesoporous silica: structures and controlled release functions as drug carrier. Mat Sci Eng C-Mater 2015; 55: 367-372
[22] Wang Y, Li W, Liu T, Xu L, Guo Y, Ke J, et al. Design and preparation of mesoporous silica carriers with chiral structures for drug release differentiation. Mat Sci Eng C-Mater 2019; 103: 109737
[23] Hu B, Wang J, Li J, Li S, Li H. Superiority of L-tartaric acid modified chiral mesoporous silica nanoparticle as a drug carrier: structure, wettability, degradation, bio-adhesion and biocompatibility. Int J Nanomed 2020; 15: 601-618
[24] De Haes W, Van Mol G, Merlin C, De Smedt SC, Vanham G, Rejman J. Internalization of mRNA lipoplexes by dendritic cells. Mol Pharmaceut 2012; 9: 2942-2949
[25] Sun J, Song Y, Lu M, Lin X, Liu Y, Zhou S, et al. Evaluation of the antitumor effect of dexamethasone palmitate and doxorubicin co-loaded liposomes modified with a sialic acid-octadecylamine conjugate. Eur J Pharm Sci 2016; 93: 177-183
[26] Lin Y-S, Haynes CL. Synthesis and characterization of biocompatible and size-tunable multifunctional porous silica nanoparticles. Chem Mater 2009; 21: 3979-3986
[27] Boegh M, Nielsen H. Mucus as a barrier to drug delivery-understanding and mimicking the barrier properties. Basic Clin Pharmacol 2015; 116: 179-186
[28] Anderski J, Mahlert L, Mulac D, Langer K. Mucus-penetrating nanoparticles: promising drug delivery systems for the photodynamic therapy of intestinal cancer. Eur J Pharm Biopharm 2018; 129: 1-9
[29] Yang X, He D, He X, Wang K, Tang J, Zou Z, et al. Synthesis of hollow mesoporous silica nanorods with controllable aspect ratios for intracellular triggered drug release in cancer cells. Acs Appl Mater Inter 2016; 8: 20558-20569
[30] Kinnear C, Moore TL, Rodriguez-Lorenzo L, Rothen-Rutishauser B, Petri-Fink A. Form follows function: nanoparticle shape and its implications for nanomedicine. Chem Rev 2017; 117: 11476-11521
[31] McMahon HT, Boucrot E. Molecular mechanism and physiological functions of clathrin-mediated endocytosis. Nat Rev Mol Cell Bio 2011; 12: 517-533
[32] Doherty GJ, McMahon HT. Mechanisms of endocytosis. Annu Rev Biochem 2009; 78: 857-902
[33] Zhao X, Wei Z, Zhao Z, Miao Y, Qiu Y, Yang W, et al. Design and development of graphene oxide nanoparticle/chitosan hybrids showing ph-sensitive surface charge-reversible ability for efficient intracellular doxorubicin delivery. Acs Appl Mater Inter 2018; 10: 6608-6617
[34] Cui L, Liu W, Liu H, Qin Q, Wu S, He S, et al. pH-Triggered charge-reversal mesoporous silica nanoparticles stabilized by chitosan oligosaccharide/carboxymethyl chitosan hybrids for effective intracellular delivery of doxorubicin. ACS Applied Bio Materials 2019; 2: 1907-1919
Similar articles: