Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an, 710049, China.
Department of Biologic and Materials Sciences, University of Michigan, Ann Arbor, MI, 48109-1078, USA.
Adv Healthc Mater. 2017 Oct;6(20). doi: 10.1002/adhm.201700630. Epub 2017 Jul 24.
Bioactive glass nanoparticles (BGNs) have attracted much attention in drug delivery and bone tissue regeneration, due to the advantages including biodegradation, high bone-bonding bioactivity, and facile large-scale fabrication. However, the wide biomedical applications of BGNs such as efficient gene delivery are limited due to their poor pore structure and easy aggregation. Herein, for the first time, this study reports novel monodispersed bioactive glass nanoclusters (BGNCs) with ultralarge mesopores (10-30 nm) and excellent miRNA delivery for accelerating critical-sized bone regeneration. BGNCs with different size (100-500 nm) are fabricated by using a branched polyethylenimine as the structure director and catalyst. BGNCs show an excellent apatite-forming ability and high biocompatibility. Importantly, BGNCs demonstrate an almost 19 times higher miRNA loading than those of conventional BGNs. Additionally, BGNCs-miRNA nanocomplexes exhibit a significantly high antienzymolysis, enhance cellular uptake and miRNA transfection efficiency, overpassing BGNs and commercial Lipofectamine 3000. BGNCs-mediated miRNA delivery significantly improves the osteogenic differentiation of bone marrow stromal stem cells in vitro and efficiently enhances bone formation in vivo. BGNCs can be a highly efficient nonviral vector for various gene therapy applications. The study may provide a novel strategy to develop highly gene-activated bioactive nanomaterials for simultaneous tissue regeneration and disease therapy.
生物活性玻璃纳米颗粒（BGNs）由于具有生物可降解性、高骨结合生物活性和易于大规模制备等优点，在药物输送和骨组织再生领域引起了广泛关注。然而，由于其较差的孔结构和易于聚集，BGNs 的广泛生物医学应用，如高效基因输送，受到限制。在此，首次报道了具有超大介孔（10-30nm）和优异 miRNA 输送能力的新型单分散生物活性玻璃纳米团簇（BGNCs），可加速临界尺寸骨再生。通过使用支化聚乙烯亚胺作为结构导向剂和催化剂，制备了不同尺寸（100-500nm）的 BGNCs。BGNCs 具有优异的成磷灰石能力和高生物相容性。重要的是，BGNCs 的 miRNA 负载量比传统 BGNs 高 19 倍。此外，BGNCs-miRNA 纳米复合物具有更高的抗酶解能力、增强细胞摄取和 miRNA 转染效率，超过了 BGNs 和商业的 Lipofectamine 3000。BGNCs 介导的 miRNA 输送可显著提高骨髓基质干细胞的体外成骨分化，并有效增强体内骨形成。BGNCs 可以成为高效的非病毒载体，用于各种基因治疗应用。该研究可能为同时进行组织再生和疾病治疗的高度基因激活生物活性纳米材料的开发提供了一种新策略。
