Near-Infrared Light-Driven Mesoporous SiO2 /Au Nanomotors for Eradication of Pseudomonas aeruginosa Biofilm.

Bacterial biofilms are linked to several diseases and cause resistant and chronic infections in immune-compromised patients. Nanomotors comprise a new field of research showing a great promise within biomedicine but pose challenges in terms of biocompatibility. Nanomotors propelled by thermophoresis could overcome this challenge, as they leave no waste product during propulsion. In this study, mesoporous-silica nanoparticles are coated with a thin layer of gold to make nanomotors, which can be driven by near-infrared (NIR) light irradiation. The prepared mesoporous SiO2 -Au nanomotors exhibit efficient self-propulsion when exposed to NIR irradiation, they penetrate deep through a biofilm matrix, and disperse the biofilm in situ due to the photothermal effect on the Au part of the nanomotors. The velocities of such nanomotors are investigated at different wavelengths and laser powers. Furthermore, the study examines the ability of these nanomotors to eradicate Pseudomonas aeruginosa (P. aeruginosa) biofilm under NIR light irradiation. The conducted study shows that the nanomotor's velocity increases with increasing laser power. The mesoporous SiO2 /Au nanomotors show excellent capabilities to eradicate P. aeruginosa biofilms even under short (30 s-3 min) irradiation time. This study shows great promise for overcoming the challenges related to bacterial biofilm eradication.

Cosmetic-Derived Mannosylerythritol Lipid-B-Phospholipid Nanoliposome: An Acid-Stabilized Carrier for Efficient Gastromucosal Delivery of Amoxicillin for In Vivo Treatment of Helicobacter pylori.

Helicobacter pylori infection is a leading cause of gastritis and peptic ulcer. Current treatments for H. pylori are limited by the increase in antibiotic-resistant strains and low drug delivery to the infection site, indicating the need for effective delivery systems of antibiotics. Although liposomes are the most successful drug delivery carriers that have already been applied commercially, their acidic stability still stands as a problem. Herein, we developed a novel nanoliposome using cosmetic raw materials of mannosylerythritol lipid-B (MEL-B), soy bean lecithin, and cholesterol, namely, LipoSC-MELB. LipoSC-MELB exhibited enhanced stability under the simulated gastric-acid condition, owing to its strong intermolecular hydrogen-bond interactions caused by the incorporation of MEL-B. Moreover, amoxicillin-loaded LipoSC-MELB (LipoSC-MELB/AMX) had a particle size of approximately 100 nm and exhibited sustained drug release under varying pH conditions (pH 3-7). Besides, LipoSC-MELB/AMX exhibited significantly higher anti-H. pylori and anti-H. pylori biofilm activity as compared with free AMX. Furthermore, LipoSC-MELB was able to carry AMX across the barriers of gastric mucus and H. pylori biofilms. Remarkably, in vivo assays indicated that LipoSC-MELB/AMX was effective in treating H. pylori infection and its associated gastritis and gastric ulcers. Overall, the findings of this study showed that LipoSC-MELB was effective for gastromucosal delivery of amoxicillin to improve its bioavailability for the treatment of H. pylori infection.

Intrinsic specificity of plain ammonium citrate carbon dots for Helicobacter pylori: Interfacial mechanism, diagnostic translation and general revelation.

The exploitation of carbon dots (CDs) is now flourishing; however, more effort is needed to overcome their lack of intrinsic specificity. Herein, instead of synthesizing novel CDs, we reinvestigated three reported CDs and discovered that plain ammonium citrate CDs (AC-CDs) exhibited surprising specificity for Helicobacter pylori. Notably, we showed that the interfacial mechanism behind this specificity was due to the affinity between the high abundant urea/ammonium transporters on H. pylori outer membrane and the surface-coordinated ammonium ions on AC-CDs. Further, we justified that ammonium sulfate-citric acid CDs also possessed H. pylori-specificity owing to their NH4 + doping. Thereby, we suggested that the incorporation of a molecule that could be actively transported by abundant membrane receptors into the precursors of CDs might serve as a basis for developing a plain CD with intrinsic specificity for H. pylori. Moreover, AC-CDs exhibited specificity towards live, dead, and multidrug-resistant H. pylori strains. Based on the specificity, we developed a microfluidics-assisted in vitro sensing approach for H. pylori, achieving a simplified, rapid and ultrasensitive detection with two procedures, shortened time within 45.0 â€‹min and a low actual limit of detection of 10.0 â€‹CFU â€‹mL-1. This work sheds light on the design of more H. pylori-specific or even bacteria-specific CDs and their realistic translation into clinical practice.

Aptamer-superparamagnetic nanoparticles capture coupling siderophore-Fe3+ scavenging actuated with carbon dots to confer an "off-on" mechanism for the ultrasensitive detection of Helicobacter pylori.

The detection of Helicobacter pylori infection in human feces is an appropriate non-invasive diagnostic method. However, the antibody-dependent stool antigen immunoassay bears many challenges. Therefore, we developed an antibody-independent biosensing platform. The core of this platform was a triple-module biosensor. The first module was Ca2+-doped superparamagnetic nanoparticles modified with an H. pylori-specific aptamer, functioning to selectively capture H. pylori cells from samples. The second module was a bifunctional co-polymer of chloroprotoporphyrin IX iron (III)-polyethylene glycol-desferrioxamine, which could bind to H. pylori with high affinity and chelate Fe3+ from the third module of Fe3+-quenched carbon dots (CDs) solution. When the formed module 1-H. pylori-module 2 complexes reacted with module 3, a subsequent magnetic separation could scavenge Fe3+, causing fluorescence recovery from quenched CDs as the transducing mechanism. This transducer could respond to tiny changes in Fe3+ concentration with distinguishable fluorescence differences, thus conferring the biosensor with high sensitivity, a wide detection range of 10-107 CFU/mL and a limit of detection (LOD) as low as 1 CFU/mL. From simulated human stool samples, H. pylori was enriched with a centrifugal microfluidic plate to eliminate any interference from matrices, and the bacteria were subjected to detection using the biosensor. The actual LOD for the biosensing platform coupling microfluidics and the biosensor was 101, and the total time taken was 65 min. This work showcases an instant, accurate, and ultra-sensitive diagnosis of H. pylori in feces.

Ureido-modified carboxymethyl chitosan-graft-stearic acid polymeric nano-micelles as a targeted delivering carrier of clarithromycin for Helicobacter pylori: Preparation and in vitro evaluation.

The effect of antibiotics in the stomach for curing Helicobacter pylori infection is hampered by the adverse gastric environment and low bioavailability of the administered drugs. Concerning these challenges, a polymeric nano-micelle was developed. Initially, carboxymethyl chitosan (CMCS) was hydrophobically modified with stearic acid (SA), and the obtained CMCS-g-SA co-polymers was further conjugated with urea to acquire U-CMCS-g-SA co-polymers. Sphere-shaped nano-micelles (UCS-NMs) with the particle sizes of approximately 200nm were obtained with the U-CMCS-g-SA co-polymers. It was specified that this nano-micelle had no cell toxicity to AGS cells, and it could maintain a stable particle size for 6h in simulated gastric fluid and for 24h in 1×PBS. Attractively, the CMCS backbones granted this nano-micelle an excellent retention time in the stomach, almost 24h; meanwhile, the grafted ureido groups conferred effective targeting to H. pylori. This nano-micelle could load clarithromycin with high efficiency and exhibited slow release of this antibiotic in a slightly alkaline environment. In vitro inhibitory assay also indicated that a significantly enhanced anti-H. pylori activity was achieved by using this nano-micelle. This work demonstrated that the U-CMCS-g-SA nano-micelle is a proper carrier for targeted delivery of clarithromycin to H. pylori under the gastric mucus layer.

Development of a fluorescence assay for highly sensitive detection of Pseudomonas aeruginosa based on an aptamer-carbon dots/graphene oxide system.

An aptamer-based fluorescence assay for culture-independent detection of Pseudomonas aeruginosa was developed. This assay was enabled by highly specific aptamers conjugated with photoluminescent carbon dots (CDs) as the fluorescent probe and graphene oxide (GO) as the quencher. Specially, high-throughput sequencing was achieved during systematic evolution of ligands via exponential enrichment (SELEX) for accurate recognition of aptamers. This assay displayed high specificity towards P. aeruginosa and was resistant to interference by other ubiquitous bacteria including Escherichia coli, Bacillus subtilis, Staphylococcus aureus, Enterococcus faecalis, and Clostridium perfringens. After the conditions were optimized, this assay achieved a wide detection range for P. aeruginosa varying from 101 CFU mL-1 to 107 CFU mL-1. Notably, it approached an excellent detection limit as low as 9 CFU mL-1. Therefore, this fluorescence assay was considered successfully developed for highly sensitive detection of P. aeruginosa. This assay also detected the contamination of P. aeruginosa in tap water and commercial bottled water, thereby suggesting its potential application in real water samples.