Gomes Fellype Diorgennes Cordeiro, Biswas Diptomit, Alves Mary Cristina Ferreira, Júnior Severino Alves, Medina Scott H
Federal University of Pernambuco, Cidade Universitária.
Pennsylvania State University.
Res Sq. 2025 Aug 6:rs.3.rs-6954848. doi: 10.21203/rs.3.rs-6954848/v1.
Surgical debridement of infected oral tissues can compromise maxillofacial aesthetics and anatomical function, thereby reinforcing the use of antibiotics as a first-line therapy. However, the escalating threat of multidrug-resistant pathogens has intensified the need for non-antibiotic alternatives that can be applied topically and eliminate microbes regardless of their resistance profiles. In this study, we introduce hybrid gallium-silver metal-organic frameworks (MOFs) as a novel therapeutic platform that integrates gallium-mediated disruption of iron-dependent metabolic pathways with the biophysical antimicrobial effects of silver nanoparticles, resulting in potent and rapid inhibition of oral streptococcal growth. Using complementary spectroscopic and microscopic techniques, we elucidate the structure and physicochemical properties of these gallium-silver MOFs, leveraging these insights to understand their antibacterial mechanisms. Cytotoxicity assays conducted on human osteogenic cells help define an appropriate therapeutic window. These proof-of-concept findings suggest that, with further optimization, gallium-silver MOFs hold promise as an attractive topical antimicrobial with potential to rapidly clear odontogenic infections.
感染性口腔组织的手术清创可能会损害颌面美观和解剖功能，因此强化了将抗生素作为一线治疗手段的应用。然而，多重耐药病原体带来的威胁不断升级，使得对可局部应用且能消除微生物（无论其耐药情况如何）的非抗生素替代品的需求日益迫切。在本研究中，我们引入了镓-银混合金属有机框架（MOF）作为一种新型治疗平台，该平台将镓介导的铁依赖性代谢途径破坏与银纳米颗粒的生物物理抗菌作用相结合，从而有效且快速地抑制口腔链球菌生长。通过互补的光谱和显微镜技术，我们阐明了这些镓-银MOF的结构和物理化学性质，并利用这些见解来理解它们的抗菌机制。对人成骨细胞进行的细胞毒性试验有助于确定合适的治疗窗口。这些概念验证结果表明，经过进一步优化，镓-银MOF有望成为一种有吸引力的局部抗菌剂，具有快速清除牙源性感染的潜力。
