Iron oxide nanozymes stabilize stannous fluoride for targeted biofilm killing and synergistic oral disease prevention.

Dental caries is the most common human disease caused by oral biofilms despite the widespread use of fluoride as the primary anticaries agent. Recently, an FDA-approved iron oxide nanoparticle (ferumoxytol, Fer) has shown to kill and degrade caries-causing biofilms through catalytic activation of hydrogen peroxide. However, Fer cannot interfere with enamel acid demineralization. Here, we show notable synergy when Fer is combined with stannous fluoride (SnF2), markedly inhibiting both biofilm accumulation and enamel damage more effectively than either alone. Unexpectedly, we discover that the stability of SnF2 is enhanced when mixed with Fer in aqueous solutions while increasing catalytic activity of Fer without any additives. Notably, Fer in combination with SnF2 is exceptionally effective in controlling dental caries in vivo, even at four times lower concentrations, without adverse effects on host tissues or oral microbiome. Our results reveal a potent therapeutic synergism using approved agents while providing facile SnF2 stabilization, to prevent a widespread oral disease with reduced fluoride exposure.

Iron oxide nanozymes stabilize stannous fluoride for targeted biofilm killing and synergistic oral disease prevention.

Dental caries (tooth decay) is the most prevalent human disease caused by oral biofilms, affecting nearly half of the global population despite increased use of fluoride, the mainstay anticaries (tooth-enamel protective) agent. Recently, an FDA-approved iron oxide nanozyme formulation (ferumoxytol, Fer) has been shown to disrupt caries-causing biofilms with high specificity via catalytic activation of hydrogen peroxide, but it is incapable of interfering with enamel acid demineralization. Here, we find notable synergy when Fer is combined with stannous fluoride (SnF 2 ), markedly inhibiting both biofilm accumulation and enamel damage more effectively than either alone. Unexpectedly, our data show that SnF 2 enhances the catalytic activity of Fer, significantly increasing reactive oxygen species (ROS) generation and antibiofilm activity. We discover that the stability of SnF 2 (unstable in water) is markedly enhanced when mixed with Fer in aqueous solutions without any additives. Further analyses reveal that Sn 2+ is bound by carboxylate groups in the carboxymethyl-dextran coating of Fer, thus stabilizing SnF 2 and boosting the catalytic activity. Notably, Fer in combination with SnF 2 is exceptionally effective in controlling dental caries in vivo , preventing enamel demineralization and cavitation altogether without adverse effects on the host tissues or causing changes in the oral microbiome diversity. The efficacy of SnF 2 is also enhanced when combined with Fer, showing comparable therapeutic effects at four times lower fluoride concentration. Enamel ultrastructure examination shows that fluoride, iron, and tin are detected in the outer layers of the enamel forming a polyion-rich film, indicating co-delivery onto the tooth surface. Overall, our results reveal a unique therapeutic synergism using approved agents that target complementary biological and physicochemical traits, while providing facile SnF 2 stabilization, to prevent a widespread oral disease more effectively with reduced fluoride exposure.

Comparative analysis of the oral microbiota between iron-deficiency anaemia (IDA) patients and healthy individuals by high-throughput sequencing.

BACKGROUND: The relationship between oral microbiota and IE (infective endocarditis) is well established. Opportunistic pathogens in normal oral flora enter the bloodstream through daily oral cleaning or invasive dental procedures, leading to the occurrence of infective endocarditis. An in vitro iron-deficient condition leads to a drastic community shift in oral microbiota with increasing proportions of taxa related to infective endocarditis. To investigate the relationship among insufficient iron supply, oral microbiota and the risk of IE and to conduct a population amplification study, iron-deficiency anaemia is used as an in vivo model. METHODS: This cross-sectional study enrolled 24 primary iron-deficiency anemia (IDA) patients from 2015.6 to 2016.6 from the hematology department of West China Hospital, Sichuan University, and 24 healthy controls. High-throughput sequencing compared the dental plaque microbiota of 24 IDA (iron-deficiency anaemia) patients and 24 healthy controls. RESULTS: Sequences were classified into 12 phyla, 28 classes, 50 orders, 161 genera and 497 OTUs (the IDA and control groups shared the same 384 OTUs). Iron deficiency leads to lower internal diversity in the oral flora. The abundances of genera Corynebacterium, Neisseria, Cardiobacterium, Capnocytophaga, and Aggregatibacter were significantly higher in healthy controls, while genera Lactococcus, Enterococcus, Lactobacillus, Pseudomonas and Moraxella showed higher proportions in the IDA group (P < 0.05). The relative abundances of genera Lactococcus, Enterococcus, Pseudomonas and Moraxella were significantly negatively correlated with the concentration of serum ferritin (P < 0.05). CONCLUSIONS: Without an increase of oral streptococci, the main pathogen of IE, it is difficult to determine whether IDA can increase the risk of IE. However, the iron-deficient condition did lead to changes in the oral microbiota community structure. The genera that showed higher proportions in the IDA group were frequently reported as antibiotic-resistant. As antibiotics are commonly recommended to prevent IE before dental procedures, this study offers new ideas of personalized prevention of IE.

TCAB1: a potential target for diagnosis and therapy of head and neck carcinomas.

BACKGROUND: WRAP53, including α, ß and γ isoforms, plays an important role not only in the stability of p53 mRNA, but also in the assembly and trafficking of the telomerase holoenzyme. It has been considered an oncogene and is thought to promote the survival of cancer cells. The aim of this study was to detect the role of TCAB1 (except WRAP53α) in the occurrence and development of head and neck carcinomas. METHODS: Immunohistochemistry was used to detect the TCAB1 expression in clinical specimen sections and performed western blotting to check the TCAB1 expression levels in cell lines. TCAB1 was depleted using shRNA lentivirus and the knockdown efficiency was assessed using q-PCR and Western blotting. We performed CCK-8 assays and flow cytometry to check the cell proliferation potential and used the trans-well assay to test the invasion ability in vitro. Xenografts were used to detect the tumor formation potential in vivo. Moreover, we performed cDNA microarray to investigate the candidate factors involved in this process. RESULTS: We observed a notable overexpression of TCAB1 in head and neck carcinoma clinical specimens as well as in carcinoma cell lines. Knockdown of TCAB1 decreased the cellular proliferation potential and invasion ability in vitro. cDNA microarray analysis suggested the possible involvement of several pathways and factors associated with tumorigenesis and carcinoma development in the TCAB1-mediated regulation of cancers. Furthermore, the xenograft assay confirmed that the depletion of TCAB1 would inhibit tumor formation in nude mice. The immunohistochemistry results of the mice tumor tissue sections revealed that the cells in shTCAB1 xenografts showed decreased proliferation potential and increased apoptotic trend, meanwhile, the angiogenesis was inhibited in the smaller tumors form shTCAB1 cells. CONCLUSIONS: Our study demonstrated that depletion of TCAB1 decreased cellular proliferation and invasion potential both in vitro and in vivo. The data indicated that TCAB1 might facilitate the occurrence and development of head and neck carcinomas. In future, TCAB1 might be useful as a prognostic biomarker or a potential target for the diagnosis and therapy of head and neck carcinomas.