Huang Regina, Zhou Zhiwen, Lan Xinmiao, Tang Fung Kit, Cheng Tianfan, Sun Hongzhe, Cham-Fai Leung Ken, Li Xuan, Jin Lijian
Faculty of Dentistry, The University of Hong Kong, Hong Kong SAR, China.
Department of Mechanical Engineering, Faculty of Engineering, The University of Hong Kong, Hong Kong SAR, China.
Mater Today Bio. 2022 Dec 1;18:100507. doi: 10.1016/j.mtbio.2022.100507. eCollection 2023 Feb.
Antibiotic resistance is a global public health threat, and urgent actions should be undertaken for developing alternative antimicrobial strategies and approaches. Notably, bismuth drugs exhibit potent antimicrobial effects on various pathogens and promising efficacy in tackling SARS-CoV-2 and related infections. As such, bismuth-based materials could precisely combat pathogenic bacteria and effectively treat the resultant infections and inflammatory diseases through a controlled release of Bi ions for targeted drug delivery. Currently, it is a great challenge to rapidly and massively manufacture bismuth-based particles, and yet there are no reports on effectively constructing such porous antimicrobial-loaded particles. Herein, we have developed two rapid approaches ( ultrasound-assisted and agitation-free methods) to synthesizing bismuth-based materials with ellipsoid- (Ellipsoids) and rod-like (Rods) morphologies respectively, and fully characterized physicochemical properties. Rods with a porous structure were confirmed as bismuth metal-organic frameworks (Bi-MOF) and aligned with the crystalline structure of CAU-17. Importantly, the formation of Rods was a 'two-step' crystallization process of growing almond-flake-like units followed by stacking into the rod-like structure. The size of Bi-MOF was precisely controlled from micro-to nano-scales by varying concentrations of metal ions and their ratio to the ligand. Moreover, both Ellipsoids and Rods showed excellent biocompatibility with human gingival fibroblasts and potent antimicrobial effects on the Gram-negative oral pathogens including , and . Both Ellipsoids and Rods at 50 μg/mL could disrupt the bacterial membranes, and particularly eliminate biofilms. This study demonstrates highly efficient and facile approaches to synthesizing bismuth-based particles. Our work could enrich the administration modalities of metallic drugs for promising antibiotic-free healthcare.
抗生素耐药性是全球公共卫生威胁，应采取紧急行动来制定替代抗菌策略和方法。值得注意的是，铋药物对多种病原体具有强大的抗菌作用，在应对严重急性呼吸综合征冠状病毒2（SARS-CoV-2）及相关感染方面有良好疗效。因此，铋基材料可通过可控释放铋离子进行靶向给药，精确对抗病原菌并有效治疗由此引发的感染和炎症性疾病。目前，快速大规模制造铋基颗粒是一项巨大挑战，且尚无关于有效构建此类负载抗菌剂的多孔颗粒的报道。在此，我们开发了两种快速方法（超声辅助法和无搅拌法）分别合成具有椭球形（椭球体）和棒状（棒体）形态的铋基材料，并对其理化性质进行了全面表征。具有多孔结构的棒体被确认为铋金属有机框架（Bi-MOF），与CAU-17的晶体结构一致。重要的是，棒体的形成是一个“两步”结晶过程，即先生长杏仁片状单元，然后堆叠成棒状结构。通过改变金属离子浓度及其与配体的比例，可将Bi-MOF的尺寸从微米精确控制到纳米尺度。此外，椭球体和棒体对人牙龈成纤维细胞均表现出优异的生物相容性，对包括牙龈卟啉单胞菌、具核梭杆菌和中间普氏菌在内的革兰氏阴性口腔病原体均有强大的抗菌作用。50μg/mL的椭球体和棒体均可破坏细菌膜，尤其能消除牙龈卟啉单胞菌生物膜。本研究展示了合成铋基颗粒的高效简便方法。我们的工作可为无抗生素医疗的金属药物给药方式提供更多选择。
