Multifunctional Thermal-responsive Bioglue Targeted at Suppurative Infection in Oral Cavity

Objective To explore association between Helicobacter pylori (Hp) infection in oral cavity and gastric Hp infection through oral cavity and gastric Hp infection testing results analysis, and also to study the effect of Hp infection in oral cavity on Hp eradication treatment. Methods Through Hp saliva test (HPS) and 13C/14C urea breath test (UBT) method, the Hp in oral cavity and stomach were tested in 114 first-visit patients with upper gastrointestinal symptoms (group 1), 129 re-visiting patients who were diagnosed gastric Hp infection with eradication treatment for four weeks (group 2) and 33 volunteers without gastrointestinal symptoms. Results The positive rates of Hp infection by HPS method were 77.19%, 75.97% and 81.82% in group 1, group 2 and group 3 respectively. There was no significant difference between these three groups (χ2=0.47, P>0.05). The positive rate of Hp infection by UBT method in group 1 (52.63%) was higher than those of group 2 (34.11%) and group 3 (21.21%). Compared group 1 with group 2 or group 3, there was significant difference (χ2=8.848, 10.19, P 0.05). In positive individuals of these three groups tested by UBT method, there was no significant difference of positive rate tested by HPS method (81.67%, 88.64% and 100% of three groups respectively, χ2=2.25, P>0.05). Conclusions The High detection of Hp antigen in saliva indicates that the oral cavity may be the second settlement of Hp beside stomach. The oral medicine haslittle effect on oral cavity Hp infection. The existence of oral Hp may be an important and direct factor of incidence and recurrent of gastric diseases. Key words: Helicobacter pylori; Mouth; Stomach; Autigens, bacterial; Saliva; Urea; Carbon radioisotopes

Background incidence of pyogenic spinal infections has increased in recent years. In addition to treating the spinal infection, optimal care also includes identifying the source of the pyogenic spinal infection and the presence of other infections. The aim of this study is to elucidate the prevalence of oral cavity infection (OCI) within this patient cohort. Methods As part of a prospective study conducted from 2016 to 2021, the number of patients with dental infections was investigated by means of an orthopantomogram (OPG) and subsequent dental examination. Results The presence of an oral infection was investigated in 55 (47%) of 118 patients by an OPG, 29 (53%) of whom had a corresponding abnormality of the oral cavity. In addition to the spinal infection, patients with an oral cavity infection revealed an increased incidence of endocarditis, sepsis and brain abscess. A spinal epidural abscess, a multilevel affection of the infection, and an elevated CRP value were also found in patients with a co-existing oral cavity infection. Back pain assessed at admission and 3 months after surgery was also more pronounced in patients with an oral cavity infection. Neurological deficits were often present in patients with spinal and oral cavity infection. Conclusions The presence of an oral cavity infection has proven to be one of the important factors in the detection of the source of the pyogenic spinal infection. In addition, a pronounced spinal affection and frequent co-infections were seen in patients with an oral cavity infection.

Mucormycosis infection is an invasive, acute and rapidly progressing fungal infection with high mortality rate unless it was identified promptly. Oral manifestations of these infections, some times appeared as palatal ulcer and can be triggered by tooth extraction on maxilla or mandibula in which the organ is not cured but even damage the gingival and alveolar bone. Hyperbaric oxygen (HBO) therapy is the administration of 100% pure oxygen in a pressurized room more than 1 atmophere that can be used for therapy of mucormycosis infection in oral cavity. The aim of this study is to analyze the use of hyperbaric oxygen therapy on mucormycosis infections in oral cavity in 30 journals and 1journal of suspected case of mucormycosis infection post dental extraction from 1980 until 2016. Hyperbaric oxygen therapy was used as the last and adjunctive therapy after antifungal and surgery in 30 jounals but in 1 suspected case, hyperbaric oxygen therapy was given earlier. The need for consideration to provide early HBO therapy in case of mucormycosis infection in oral cavity will improve prognosis and survival rate of the patient.

To assess the association between periodontal disease and Helicobacter pylori (H. pylori) infection in oral cavity. We searched PubMed, Embase, Web of Science, Cochrane library, Gray literature, and clinicaltrials.gov for eligible studies up to September 25, 2019. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. The random-effects model was used with the software STATA 13.0. The Newcastle-Ottawa-Scale was used for quality evaluation. Twelve observational studies (eight from Asia, one from Europe, and three from the South America) involving 2727 participants were included in the meta-analysis. The overall pooled results showed that H. pylori infection in oral cavity was associated with periodontal disease (OR 2.53, 95% CI 1.86-3.44, P < 0.05). No significant heterogeneity among the articles was observed (I2 = 44.3%, P < 0.05). The sensitivity analysis indicated that the result of our meta-analysis was generally stable. The Begg test and the Egger test both showed no publication bias was observed (P = 0.45 and P = 0.18 respectively). Based on current available evidence, it seemed there was a correlation between oral H. pylori infection and the occurrence of periodontal disease. However, since most of the data comes from Asia, more large-scale investigations with high quality from all over the world are needed to confirm the association. H. pylori infection in oral may have a positive association with the prevalence of periodontal disease mainly in Asian populations.

Summary The aim of this study was to evaluate the antimicrobial activity of propolis samples collected from different regions of Turkey against anaerobic bacteria causing especially oral cavity infections. A total of eleven anaerobic bacterial strains have been tested in this study. The strains were tested by agar dilution method for detecting minimum inhibitory concentration (MIC) and by macro dilution broth method for detecting minimum bactericidal concentration (MBC). Turkish propolis samples were found highly effective against all tested anaerobic bacteria compared with ethanol control, without statistical differences. The MIC and MBC of propolis samples ranged from 0.40.6 mg/ml to 108.1-186.2 mg/ml, respectively. Actinomyces odontolyticus was the most susceptible strains; whereas Prevotella intermedia was was the least susceptible strain to all tested propolis samples. Ilic/Erzincan (ER-I) propolis sample was the more effective against all tested anaerobic bacteria; whereas Bartin (BA) propolis sample was the less effective. Gram-positive anaerobic bacteria were detected to be the most sensitive to propolis samples; with the MIC values ranging from 0.4 to 6.1 mg/ml compared with Gram-negative anaerobic bacteria with MIC ranging from 5.8 to 108.1 mg/ml (P<0.05). As a result of, Turkish propolis samples had antibacterial activity against anaerobic bacteria especially causing oral cavity infections. Because of the high rate of resistance of the anaerobic bacteria isolated from oral cavity infections, standardized preparations of propolis are suggested to use in treatment of this kind of infections. However, further studies are needed to be performed on the clinical applications of propolis in oral cavity infections.

The incidence of pyogenic spondylodiscitis is increasing; however, the source of infection often remains obscure. We analyzed predisposing factors, pathogens, and outcome of patients undergoing surgical and/or conservative treatment of spondylodiscitis with a focus on the diagnostic work-up including a comprehensive maxillofacial assessment. The analysis of prognostic factors comprised comorbidities, nicotine dependence, symptom duration, and oral cavity peculiarities. After a standardized diagnostic work-up, a detailed examination of the oral cavity was also performed. The outcome analysis included assessment of the patients' clinical status. Forty-one patients with pyogenic spondylodiscitis were investigated of whom 24% had undergone spinal surgery within 4 weeks before the infection. A total of 29% of patients were found to have a concomitant bacterial oral cavity disease, and in 22% the definitive source of infection remained unidentified. Among the 12 patients with oral cavity infections, 10 patients had periodontitis; 8, root canal pathologies; 6, periapical lesions, and another 8 patients, caries. In 25% of these patients, typical oral cavity pathogens were found in the intervertebral disk. The prevalence of oral cavity infections was associated with a history of nicotine dependence (p = 0.003). All other analyzed comorbidities did not differ compared with patients without an oral cavity focus. Oral cavity infections appear to be a frequent source of pyogenic spondylodiscitis, with smoking its most relevant associated risk factor. In case of an unidentified infection focus, a detailed diagnostic work-up including a mandatory maxillofacial assessment is strongly recommended.

Human papillomavirus (HPV) is associated with several types of oral lesions (OLs), including oropharyngeal squamous cell carcinoma (SCC), especially in HIV-positive individuals. To identify the prevalence and clinical implications of the alpha (α) and beta (β) genera of HPV in the oral cavity and oropharynx of HIV-positive men who have sex with men (MSM). A cross-sectional study from January 2022 to May 2023 was performed. Ninety-four participants were included; their sexual habits, risk factors, HIV-1 viral load, and CD4+ T-cell counts were obtained. Exfoliative cytology was performed, and deoxyribonucleic acid (DNA) was extracted from the samples to identify α and β HPV genera through endpoint polymerase chain reaction (PCR). OLs associated with HPV infection were described, and histopathological and immunohistochemical findings for p16 were reported. A total of 71.3% of the participants were positive for any HPV genus (22.4% α-HPV and 49.2% β-HPV). The 6.3% had OLs associated with HPV, principally leukoplakia, and although six of nine samples were p16 positive, none were malignant. The prevalence of HPV infection in the oral cavity and oropharynx in HIV + MSM was high; however, the associated OLs were infrequent and not malignant. Future studies are necessary to evaluate the clinical relevance of HPV infection and p16-positive OLs.

Bioadhesive polymeric nanoparticles as strategy to improve the treatment of yeast infections in oral cavity: in-vitro and ex-vivo studies

Aim. To establish the association between the presence of chronic infection in oral cavity and the severity of SARSCoV-2 infection.Materials and methods. The study was conducted among 30 people aged between18 and 22 who had had coronavirus infection from mild to severe cases. The assessment of oral health was carried out with main and additional examination methods, CFE index, PMA index, Greene, Wermillion oral hygiene index.Results. In group 1, the average value of CFE index was 4.2, in the second group – CFE index was twice higher at 7.8. PMA index in patients of group 2 was significantly higher (p&gt; 0.01) and was at the level of 41.5%. In group 1, the PMA index was 13.3%. It was found that 17% of the respondents in the control group and 70% patients in the experimental group had an episodic exacerbation of dental diseases during COVID-19.Conclusions. The data obtained indicates a correlation between oral diseases and the severity of COVID-19. It is necessary to consider that chronic infection in the oral cavity as well as poor oral hygiene can act as a risk of complications of viral infections, in particular, of COVID-19.

This work evaluated the HPV infection in the oral cavity (using oroscopy and exfoliative oral cytology) and its relation to genital infection in women with cytological diagnosis suggestive of HPV infection. The sample consisted of 60 patients who underwent oroscopy, cytology and viral determination in mouth and cervix by PCR using generic primers MY09/MY11 and MPCR. HPV DNA was detected in oral and genital mucosa in 48.33% and 73.3% of patients, respectively, yielding a concordance of 44.2% (k=0.44, moderate agreement). The most common viral types were low risk, especially type 6, found in 86.2% of oral samples and 65.9% of cervical specimens, alone or in combination with other types of low (11) or high oncogenic risk (16, 18, 33), with a concordance of 10.45% (k = 0.1, insignificant agreement). However, in relation to the type 6, there was a concordance of 75.86% (k=0.7, high agreement). The cytology of the oral cavity had a sensitivity of 3.5% and a specificity of 93.6%. For oroscopy, sensitivity was 27.6% and specificity of 74.2%. The results indicate that HPV infection in oral cavity of patients with genital infection could be frequent. The low concordance between HPV types suggests that HPV infection in the mouth and cervix has a different biological behavior.

Oral Viral Infections: Diagnosis and Management

Background: Areca nut (Areca catechu L.) and red ginger (Zingiber officinale Rosc. var. rubrum) are herbal plants that have specific phytochemical compound functional groups that have the potential to be used as antifungal and antibacterial. However, the optimal effect of the combination of the two extracts against oral candidiasis and oral bacterial infections is not yet known with certainty. This study aims to evaluate the effect of the combination of areca nut and red ginger on the development of microbial infection in oral cavity. Methods: Plant extraction is carried out using the maceration method. Functional group test using an FTIR spectrophotometer. The antifungal assay with Candida albicans (C. albicans) ATCC 10231 using well-diffusion technique on sabouraud dextrose agar media. Comparison of concentrations of areca nut: red ginger combination is 80%:20%, 50%:50%, and 20%:80%, respectively. The disc diffusion method was used to determine the antimicrobial activities against Staphylococcus aureus (S. aureus). Data analysis of antifungal assay was carried out using the Kruskall-Wallis test with p&lt;0.05, post-hoc using the Mann-Whitney test, and the antibacterial activity using one-way ANOVA with p&lt;0.05 and post-hoc using LSD test. Results: The areca nut extract confirmed the presence of the phenolic, alcohol, and aromatic benzene compounds. The red ginger contained flavonoid, alkaloid, and aromatic functional groups. The combination of areca nut and red ginger extract with a concentration ratio of 80%:20% had the highest inhibitory activity against C. albicans; 15.13±1.71mm with the positive control being 12.43±1.40 mm. In the antibacterial activity, the combination of 80%:20% areca nut and red ginger extract has an average inhibition zone of 12.43±1.40 mm which is the strongest inhibition ability while the positive control is 11.21±2.62 mm. Conclusion. The combination of areca nut and red ginger extracts contained potential phytochemical compounds that influence the antimicrobial ability. The concentration ratio of 80%:20% of areca nut and red ginger extract has the strongest inhibitory activity against C. albicans and S. aureus.

Introduction: Many infections of the oral cavity and adjacent structures involve anaerobic bacteria. Most infections involve multiple anaerobes and in many instances facultative organisms. Present study was conducted regarding to clinical aspects and complications of anaerobic bacterial infections in oral cavity. Materials and Methods: 72 Specimens were taken from oral cavity infections. Routine culture techniques and strict anaerobic techniques were used for isolation and identification of aerobic, facultative and obligatory anaerobic bacteria respectively. Results: Cultures of all specimens were positive. Mono- bacterial and poly bacterial infections were repored in 1/3 and 2/3 of specimens, respectively. More than 65% of isolated organisms, were obligatory anaerobic belonging to the Peptostreptococcus, Prevotella, Fusobacterium, Porphyromonas and Bacteriodes as well as facultative and aerobic species include Streptococcus, Staphylococcus , interobacteriacea and Actinomcs Israelii are also obtained. Conclusion: Many infections of the oral cavity and adjacent structures involve obligatory anaerobic bacteria. Regarding to results of present study, under the anaerobic atmospheric system, obligatory anaerobic bacteria were isolated and identified from clinical specimens of oral cavity infections, especially abscesses.

Oral health is a major concern in Indonesia, which is caused by bacteria infections in oral cavity.¹ Bacteria such as Staphylococcus play a crucial role in the development of dental diseases, showing the need for improving oral hygiene to prevent infections.² Therefore, this research aimed to evaluate the effectiveness of mackerel fish oil (Rastrelliger sp.) emulgel against Staphylococcus aureus using the disk diffusion method in an in vitro. The investigation was carried out using an experimental laboratory design with a post-test only control group through the Kirby-Bauer disk diffusion method. The samples consisted of various concentrations of mackerel fish oil emulgel (10, 5, 2.5, 1.25, 0.62, and 0.31%). Clinium® gel 1% was used as a positive control, while gel base was served as a negative control. The formation of inhibition zone diameter after 24 hours of incubation was measured in millimeters (mm) using a vernier caliper. The results showed that mackerel fish oil (Rastrelliger sp.) emulgel had antibacterial activity against Staphylococcus aureus. The mean inhibition zone diameters observed at concentrations 10, 5, 2.5, 1.25, 0.62, and 0.31% were 16.99 mm, 13.23 mm, 10.32 mm, 7.18 mm, and 6.23 mm. Mackerel fish oil (Rastrelliger sp.) emulgel showed effective antibacterial activity against Staphylococcus aureus in an in vitro setting.

Open AccessCCS ChemistryRESEARCH ARTICLE3 Oct 2022Supramolecular Polymerization Powered by Escherichia coli: Fabricating a Near-Infrared Photothermal Antibacterial Agent in Situ Zihe Yin, Yuchong Yang, Jinpeng Yang, Guobin Song, Hao Hu, Peng Zheng and Jiang-Fei Xu Zihe Yin Key Lab of Organic Optoelectronics and Molecular Engineering, Department of Chemistry, Tsinghua University, Beijing 100084 Google Scholar More articles by this author , Yuchong Yang Key Lab of Organic Optoelectronics and Molecular Engineering, Department of Chemistry, Tsinghua University, Beijing 100084 Google Scholar More articles by this author , Jinpeng Yang Key Lab of Organic Optoelectronics and Molecular Engineering, Department of Chemistry, Tsinghua University, Beijing 100084 Google Scholar More articles by this author , Guobin Song State Key Laboratory of Coordination Chemistry, Chemistry and Biomedicine Innovation Center (ChemBIC), School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023 Google Scholar More articles by this author , Hao Hu Key Lab of Organic Optoelectronics and Molecular Engineering, Department of Chemistry, Tsinghua University, Beijing 100084 Google Scholar More articles by this author , Peng Zheng State Key Laboratory of Coordination Chemistry, Chemistry and Biomedicine Innovation Center (ChemBIC), School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023 Google Scholar More articles by this author and Jiang-Fei Xu *Corresponding author: E-mail Address: [email protected] Key Lab of Organic Optoelectronics and Molecular Engineering, Department of Chemistry, Tsinghua University, Beijing 100084 Google Scholar More articles by this author https://doi.org/10.31635/ccschem.021.202101490 SectionsSupplemental MaterialAboutAbstractPDF ToolsAdd to favoritesDownload CitationsTrack Citations ShareFacebookTwitterLinked InEmail An Escherichia coli reduction-powered supramolecular polymerization is reported, leading to the fabrication of a near-infrared (NIR) photothermal antibacterial agent in situ. To this end, a bifunctional monomer containing two viologen moieties was designed. When incubating E. coli with the bifunctional monomer and cucurbit[8]uril, viologen moieties were reduced to viologen cation radicals by E. coli, and a supramolecular polymer with supramolecular dimers of viologen cation radicals integrated into the main chain was fabricated on the surface of E. coli. The NIR photothermal conversion property of the supramolecular dimer of viologencation radicals endowed the supramolecular polymer with photothermal antibacterial ability, and this performance was further improved by the local enrichment effect of supramolecular polymers and their enhanced adsorption onto the bacteria surface. Moreover, only certain bacteria, such as E. coli, possess the reducing ability to power supramolecular polymerization, whereas many other bacteria, such as Bacillus subtilis, Pseudomonas aeruginosa, and Staphylococcus aureus, do not possess this ability. Therefore, the supramolecular polymer exhibits outstanding bacterial inhibition efficiency (>99.9%) with high specificity toward E. coli under 1064 nm NIR irradiation. It is anticipated that this biologically powered in situ supramolecular polymerization strategy presents great potential in fabricating smart biomedical supramolecular materials with adaptivity and programmability. Download figure Download PowerPoint Introduction In an out-of-equilibrium biological system, many metabolic activities and physiological functions are energy-consuming processes. For bacteria, a transmembrane redox potential generated by procaryote respiration not only supports biological functions,1,2 but also can be employed as an energy source for various artificial applications, such as bioelectrosynthesis, initiation of polymerization, and microbial fuel cells.3–10 Notably, the reducing ability of bacteria originating from this redox potential has been applied to the in situ fabrication of biomedical materials at the places where they function.7,8,11 Compared with conventional biomedical materials, which are generally readily constructed and then transported to the working area, in an in situ fabrication strategy, the targeting ability could be realized, and then the transporting process could be omitted, thus improving the specificity and adaptivity of biomedical materials.12–17 As an integration of polymer science and supramolecular chemistry, supramolecular polymers exhibit superiority in various biomedical applications18–25 such as drug delivery,26–30 bioimaging and diagnosis,31,32 phototherapy,33–35 and tissue engineering.36–38 If supramolecular polymerization could be implemented in biological environments, biodegradability and stimuli-responsiveness originating from the dynamic and reversible noncovalent interactions may be imparted to the supramolecular biomedical materials that are fabricated in situ. Therefore, we wondered whether the reducing ability of bacteria could be utilized to power a supramolecular polymerization process. Our design idea arises from the fact that some electron-deficient dyes with large π-conjugated structures can be reduced to organic free radicals in a local reducing environment produced by some facultative anaerobic bacteria such as Escherichia coli.11,39,40 On the one hand, the self-assembly of these organic free radicals into supramolecular free radicals may serve as the driving force for supramolecular polymerization.41–50 On the other hand, supramolecular free radicals are expected to possess remarkable near-infrared (NIR) absorption,51–54 which may endow the supramolecular polymers with an outstanding photothermal conversion property and photothermal antibacterial performance. Therefore, by integrating the formation of NIR photothermal conversion motifs into a bacteria-powered supramolecular polymerization process, NIR photothermal antibacterial supramolecular polymers are hopeful to be constructed. Such an antibacterial agent would be selectively activated by the reduction with E. coli, whereas it could exactly kill thebacteria that induced the activation before. Such a “suicide” process of the bacteria may impart high antibacterial specificity to the agent. To this end, we designed and synthesized a bifunctional monomer named isviologen-diazabicyclo[2.2.2]octane-viologen (VDV), which contained two viologen moieties as end groups linked by a rigid and positively charged 1,4-diazabicyclo[2.2.2]octane unit. It was discovered that E. coli possessed the ability for reducing viologen into viologen cation radical under anaerobic conditions. As shown in Schemes 1a and 1b, when incubating E. coli with equimolar amounts of VDV and cucurbit[8]uril (CB[8]), the viologen moieties could be reduced to viologen cation radicals, and an in situ supramolecular polymerization could occur driven by the 2:1 host–guest complexation between viologen cation radicals and CB[8], generating a supramolecular polymer (VR-SP) with supramolecular dimers of viologen cation radicals integrated into the main chain. Moreover, the supramolecular dimer of viologen cation radicals exhibited absorption at the NIR biowindow, which might endow the VR-SP with photothermal antibacterial activity. By forming such an NIR photothermal antibacterial agent, E. coli could be killed by the local increase in temperature under NIR irradiation. This photothermal therapy is a powerful antimicrobial method with high penetration depth, few side effects, and low risk in generating drug resistance.55–71 Furthermore, the photothermal antibacterial efficiency could be enhanced significantly by the local enrichment effect of supramolecular polymers and their enhanced adsorption onto the surface of bacteria, since the positively charged VR-SP would exhibit strong interactions with the negatively charged surface of the bacteria. In addition, after completely inhibiting E. coli, VR-SP would be spontaneously degraded, as the viologen cation radicals are easily oxidized (commonly by oxygen) without the continuous reduction powered by living bacteria, thus turning off the antibacterial activity automatically. We therefore envisioned that, based on the supramolecular polymerization powered by E. coli, an NIR photothermal antibacterial agent with high antibacterial efficiency, specificity, and degradability could be fabricated in situ. Scheme 1 | (a) Chemical structures of the bifunctional monomer VDV, CB[8], and the supramolecular dimer of viologen cation radicals, and a graphic representation of the photothermal antibacterial supramolecular polymer VR-SP. (b) A schematic representation for the photothermal therapy using an NIR photothermal antibacterial agent fabricated through in situ supramolecular polymerization powered by E. coli. Download figure Download PowerPoint Experimental Method Unless otherwise noted, materials were obtained from commercial suppliers and were used without further purification. All types of bacteria were grown in Luria–Bertani (LB) culture medium at 37 °C for 8 h before further application. The detailed synthetic routes of VDV and 1-methyl-1′-(3-(trimethylammonio)propyl)-viologen tribromide (VMA), as well as detailed experimental methods are shown in Supporting Information. UV–vis spectra were measured using a HITACHI UH4150 spectrophotometer (Hitachi, Ltd., Tokyo, Japan) or a GE Ultrospec9000 spectrophotometer (General Electric Company, Boston, Massachusetts, United States). VDV (0.20 mM), or VDV (0.20 mM) and CB[8] (0.20 mM) were dissolved in LB medium. Then, 3.5 mL LB medium with dissolved agent was transferred into a quartz cuvette (1.00 cm). Then 100 μL of the suspension of bacteria (E. coli, Bacillus subtilis, Enterococcus faecalis, Staphylococcus aureus, or Pseudomonas aeruginosa) was added. The samples were sealed and incubated at 37 °C for 20 h, and then the UV–vis spectra were recorded. Electron paramagnetic resonance (EPR) spectra were obtained using a JEOL JES-FA200 spectrometer. VDV (0.20 mM), or VDV (0.20 mM) and CB[8] (0.20 mM) were dissolved in LB medium. Then 100 μL of the suspension of bacteria (E. coli or B. subtilis) was added into 3.5 mL LB medium with dissolved agent. The medium was blown by a pipette and transferred into a capillary tube (Φ = 0.5 mm). After being filled with the medium, the capillary tube was sealed by melted paraffin. The samples were incubated at 37 °C for 40 h and then measured with the EPR spectrometer. The redox potential of VDV and VDV-CB[8] was measured by differential pulse voltammetry. The differential pulse voltammetry measurements were carried out with the three-electrode system using a CHI660E electrochemical workstation (CH Instruments, Inc., Austin, Texas, United States). A glass carbon disk (0.07 cm2) was applied as the working electrode with a Pt counter electrode and a saturated Ag/AgCl electrode (KCl saturated) reference electrode. The working electrode was polished with 0.3 and 0.05 μm alumina (Al2O3) successively and washed with deionized water before use. NaCl solution (50 mM) was used as supporting electrolyte. After degassing by passing N2 through the solution for at least 30 min, differential pulse voltammetry measurements were conducted on VDV (0.20 mM), or VDV (0.20 mM) and CB[8] (0.20 mM) solution. The redox potential of the bacterial cultural medium was measured using a hand-held ORP probe (Shanghai Sanxin SX712). The E. coli suspension (15 μL) was added into a cuvette containing LB medium (2 mL). The composite electrode of the ORP probe (using saturated Ag/AgCl electrode as reference electrode) was also immersed in the medium to monitor redox potential changes. The cuvette was sealed to prevent interference from air, and the bacteria were then incubated at 37 °C for 12 h. After that, the redox potential of the medium of E. coli was detected. For E. faecalis, S. aureus, B. subtilis, and P. aeruginosa, the redox potential was measured with the same method. A Nanowizard 4 atomic force microscopy (AFM; JPK, Berlin, Germany) coupled to an inverted microscope (Olympus IX73, Olympus Corporation, Tokyo, Japan) was used to perform the AFM imaging on live E. coli. The AFM was equipped with a cell-culture chamber to keep the temperature appropriate for E. coli (37 ± 1 °C). And a poly-d-lysine-coated mica disc was used as the substrate for E. coli immobilization and subsequent imaging. A PFQMN-Lc-A-CAL AFM cantilever (Bruker Corporation, Billerica, Massachusetts, United States) with a nominal spring constant of 0.1 N/m was used. For detailed scanning parameters and sample preparation procedures, please refer to Supporting Information. An FC-1064-3000-MM Laser Light Source (Wavicle Laser) was applied to produce a 1064 nm NIR laser in the photothermal therapy under NIR irradiation, and the NIR laser-induced heat experimental phenomenon was recorded by a Fluke Ti450 Infrared Camera. VDV (0.20 mM), or VDV (0.20 mM) and CB[8] (0.20 mM), or VMA (0.40 mM) and CB[8] (0.20 mM) were dissolved in LB medium, and 3.5 mL LB medium with dissolved agents was transferred into a quartz cuvette (for control group, LB medium without dissolved agent was applied). Then 30 μL of the suspension of bacteria (E. coli or B. subtilis) was added. The samples were sealed and incubated at 37 °C for 20 h. After incubation, the samples were irradiated by a 1064 nm NIR laser (2.0 W/cm2) for 12.5 min at 37 °C, and the temperature of the cuvette was recorded by Fluke Ti450 Infrared Camera every 2.5 min. The inhibition ratio was determined by calculating the number of colony-forming units (CFUs). The cell viability of both BEAS-2B and NCM460 cells was measured in vitro by the Cell Counting Kit-8 (CCK-8) assay. The cells were planted in 96-well plates with a density of about 5 × 103–8 × 103 cells per well for 24 h. Then the cells were treated with the medium containing equimolar amounts of VDV and CB[8] or VDV alone ranging from 0.10 to 0.40 mM for 24 h. After that, the cells were treated with fresh medium containing CCK-8 for 1 h to replace the previous medium. A microplate reader (EnVision, PerkinElmer, Inc., Waltham, Massachusetts, United States) was used for the measurement of absorbance at 450 nm, which was applied to calculate the cell viability. For detailed cell culture conditions, please refer to Supporting Information. Results and Discussion The formation of viologen cation radicals from VDV by E. coli reduction was characterized by UV–vis spectroscopy. As shown in Figure 1a, when incubating E. coli with VDV or equimolar amounts of VDV and CB[8] for 12–20 h, the color of the solution changed from light yellow to blue or dark violet, which are the characteristic colors of viologen cation radical monomer or supramolecular dimer of viologen cation radicals, respectively. With the existence of CB[8], absorption bands ranging from the UV to the NIR regionpeaking at 366, 542, and 872 nm were observed, which were attributed to the characteristic absorption of the supramolecular dimer of viologen cation radicals. In contrast, the characteristic absorption peaks of viologen cation radical monomer at 396 and 601 nm were observed in the absence of CB[8]. These results suggest the formation of viologen cation radicals. Figure 1 | (a) UV–vis spectra and images of the solution of VDV with or without CB[8] after incubating with E. coli at 37 °C for 20 h. (b) EPR spectra of VDV with or without CB[8] after incubating with E. coli at 37 °C for 40 h. (c and d) UV–vis spectra and images of the solution of VDV and CB[8] after incubating with E. coli, E. faecalis, B. subtilis, P. aeruginosa, or S. aureus at 37 °C for 20 h (VDV: 0.20 mM, CB[8]: 0.20 mM, medium: LB medium). Download figure Download PowerPoint The generation of viologen cation radicals by E. coli reduction was further confirmed by EPR. As shown in Figure 1b, an EPR signal with g factor of 2.0034 was observed after incubating E. coli with VDV. When incubating E. coli with equimolar amounts of VDV and CB[8], an EPR signal with the same g factor but significantly lower intensity was observed. Given that no EPR signal was observed when incubating E. coli without any additives, the observed signals were ascribed to viologen cation radical monomer; the lower signal intensity observed in the presence of CB[8] indicated that most of the generated viologen cation radicals self-assembled with CB[8] to form the supramolecular dimer of viologen cation radicals.48,72 In contrast, no EPR signal was observed when incubating VDV or VDV-CB[8] with aerobic bacteria B. subtilis, indicating the negligible reducing ability of B. subtilis to viologen ( Supporting Information Figure S10). To understand whether E. coli was the only bacteria possessing the reducing ability, five types of bacteria including E. coli, E. faecalis, B. subtilis, S. aureus, and P. aeruginosa were incubated with VDV-CB[8], and UV–vis spectra were recorded after 20 h incubation. As shown in Figure 1c, only E. coli presented remarkable reducing ability to generate viologen cation radicals. E. faecalis showed a much weaker reducing capacity than E. coli. For the other three types of bacteria, no absorption of viologen cation radicals was observed (Figure 1d), indicating their low reducing ability. To study the reducing ability of different types of bacteria quantitatively, the redox potential of the medium of different types of bacteria after incubation was measured. As shown in Table 1, the redox potential of E. coli culture medium reached as low as −551 mV. As for E. faecalis, the redox potential of the medium was −429 mV. The other bacteria media exhibited higher redox potential (Table 1). Compared with the first one-electron reduction potential of VDV (−558 mV) and VDV-CB[8] (−481 mV) measured by differential pulse voltammetry ( Supporting Information Figure S12), we judged that E. coli could reduce VDV to generate viologen cation radicals with or without CB[8]. E. faecalis could only reduce a small proportion of VDV with the existence of CB[8], whereas the other three types of bacteria could not reduce VDV. All the above results reveal that only E. coli possesses the remarkable reducing ability to generate viologen cation radicals, and the viologen cation radicals self-assemble into supramolecular dimer of viologen cation radicals in the presence of CB[8]. Table 1 | The Redox Potential of the Medium of Different Types of Bacteria after Incubationa Bacteria Redox Potential (mV) E. coli −551 E. faecalis −429 B. subtilis −171 P. aeruginosa −289 S. aureus −300 aAll redox potential values were measured related to saturated Ag/AgCl electrode. The formation of supramolecular polymers in solution driven by the host–guest complexation between viologen cation radicals and CB[8] was investigated by diffusion-ordered NMR spectroscopy (DOSY). Equimolar amounts of VDV and CB[8] were dissolved in D2O and then VDV was reduced via a photoinduced electron transfer process under 254 nm UV irradiation. After the complete reduction of viologen moieties, the diffusion coefficient of the species in solution measured by DOSY decreased significantly from 1.80 × 10−10 to 6.35 × 10−11 m2·s−1, indicating the formation of supramolecular polymers. According to the Stokes–Einstein equation, the degree of polymerization (DP) was approximately 23 (see Supporting Information). This result indicates that VR-SP is formed in aqueous solution successfully. To investigate whether VR-SP could be fabricated and adsorbed on the surface of E. coli, AFM imaging was employed. E. coli was incubated with equimolar amounts of VDV and CB[8] for 20 h to prepare VR-SP on the surface. After the color of the medium changed from light yellow to dark violet, E. coli was transferred into the petri dish, and fixed onto a poly-d-lysine coated mica disc. After that, E. coli was imaged directly by AFM. Compared with the untreated E. coli shown in Figure 2a, the edge of the E. coli incubated with VDV-CB[8] was uneven, as shown in Figures 2b, 2c, and 2e, suggesting the formation and adsorption of supramolecular polymers on the surface of E. coli. To further support that the adsorbed supramolecular polymers were responsible for the observed uneven edge of E. coli, the buffer in culture dish with the imaged bacteria in Figure 2c was carefully replaced by phosphate-buffered saline (PBS) without disturbing the bacteria. As shown in Figures 2d and 2f, the E. coli again exhibited the smooth edge, which could be explained as the oxidation of VR-SP by air; therefore, the adsorbed supramolecular polymers were degraded. Considering that VDV alone could not lead to the uneven edges of bacteria ( Supporting Information Figure S17), AFM observations suggest that VR-SP is formed and adsorbed on the surface of bacteria. Figure 2 | AFM images of (a) untreated E. coli and (b and c) E. coli incubated with 0.20 mM VDV and 0.20 mM CB[8]. (d) AFM image of the E. coli in image (c) after replacing the solution in the petri dish with PBS buffer. (e) Magnified image of the labeled area in (c). (f) Magnified image of the labeled area in (d). Download figure Download PowerPoint The DP of VR-SP generated on the surface of E. coli was further estimated by end-group analysis measured by EPR. Viologen cation radical monomer, which is the end group of VR-SP, can be characterized by EPR, whereas the supramolecular dimer of viologen cation radicals exhibits no EPR signal. Combining the EPR measurements of E. coli with VR-SP adsorption and viologen cation radical monomer, the DP of VR-SP was estimated to be approximately 17 (see Supporting Information). In comparison, the DP of the supramolecular polymer formed in aqueous solution at the same concentration was also measured by the end-group analysis using EPR, which was estimated to be approximately 21. This result indicated that VR-SP could be formed on the surface of E. coli though the bacteria surface might disturb the host–guest complexation between viologen cation radical and CB[8] a little. Therefore, by combining the AFM imaging and end-group analysis, we conclude that supramolecular polymers can be fabricated on the surface of bacteria through in situ supramolecular polymerization powered by E. coli. Based on the E. coli-powered supramolecular polymerization in situ, and the NIR absorption of the supramolecular dimer of viologen cation radicals, we further explored the bacterial inhibition activity of VR-SP by photothermal therapy. The photothermal conversion property of VR-SP prepared by chemical reduction was first studied. As shown in Supporting Information Figure S19, a significant temperature increase of VR-SP solutionwas observed under 1064 nm irradiation at the second NIR (NIR-II) window, indicating the effective photothermal conversion of VR-SP. The photothermal conversion efficiency was 22.0% (see Supporting Information). Next, the photothermal antibacterial experiments were conducted. As shown in Figures 3a and 3b, under NIR irradiation at 1064 nm, the temperature of the medium with VR-SP adsorbed E. coli increased significantly. It rose from to °C after 12.5 min irradiation, indicating that VR-SP energy into When E. coli was incubated with VDV the increase of temperature was lower than the VR-SP group after irradiation for the same When E. coli was treated with viologen VMA (Figure and CB[8], which could be reduced to generate supramolecular dimer of viologen cation radicals but not supramolecular the temperature increase was to that of the control group without any agent under the same irradiation The significantly higher temperature increase of the VR-SP group could be ascribed to the local enrichment and enhanced adsorption of VR-SP onto the surface of E. coli. As shown in Supporting Information Table the potential of E. coli significantly increased from of untreated E. coli to when incubated with equimolar amounts of VDV and CB[8]. As a comparison, when incubated with only VDV, the potential increased to mV. These results that the adsorption of VR-SP onto the surface of E. coli is higher than that of VDV of the of of supramolecular polymers. As for bacteria with low reducing ability, B. subtilis for since no viologen cation radicals were generated and no supramolecular polymers could be the increase of temperature was after irradiation in the presence or absence of VDV-CB[8] °C or °C with or without VDV-CB[8], The results of these groups that the of VR-SP is to a higher temperature in photothermal therapy. Figure | (a) of the medium with E. coli or B. subtilis, or with E. coli or B. subtilis treated with different agents under irradiation. (b) images of the medium with E. coli or B. subtilis, or with E. coli or B. subtilis treated with different agents after 12.5 min irradiation. (c) The chemical of VMA (VDV: 0.20 mM, CB[8]: 0.20 mM, 0.40 mM, medium: LB medium). Download figure Download PowerPoint The antibacterial activity was by of As shown in Figure the inhibition efficiency of VR-SP to E. coli was after 12.5 min of 1064 nm irradiation, which was significantly higher than that of VDV and In contrast, equimolar amounts of VDV and CB[8] exhibited no inhibition of B. subtilis after irradiation under the same since no supramolecular polymers were It is that after 12.5 min irradiation under air, the absorption peaks of supramolecular dimer of viologen cation radicals in the UV–vis ( Supporting Information Figure and the EPR signal of viologen cation radicals ( Supporting Information Figure both of which the of VR-SP after the inhibition of E. coli. This is since E. coli reduce viologen to prevent the Therefore, these results that VR-SP is an NIR photothermal antibacterial agent with outstanding bacterial inhibition efficiency, high specificity E. coli, and Figure 4 | ratio of E. coli or B. subtilis incubated with or without different agents after 12.5 min irradiation figure of the ratio of VR-SP adsorbed E. coli group shown are ± from = = by the with the E. coli or B. subtilis group without any or Download figure Download PowerPoint To the of VR-SP as biological materials, the of equimolar amounts of VDV and CB[8] on cells was To this end, cell BEAS-2B and cell NCM460 were as As shown in Figures and when treated with equimolar amounts of VDV and CB[8] ranging from 0.10 to 0.40 mM, the cell viability of both BEAS-2B cell and NCM460 cell measured by CCK-8 was A was also observed on the cells treated with VDV alone ( Supporting Information Figure Therefore, VDV-CB[8] VDV alone exhibited at a high concentration (0.40 mM), which was the concentration used in antibacterial Therefore, VR-SP may be a potential agent for photothermal therapy. Figure 5 | of equimolar amounts of VDV and CB[8] to (a) BEAS-2B cell and (b) NCM460 Download figure Download PowerPoint We fabricated an NIR photothermal antibacterial agent through E. coli