The escalating global threat of antibiotic resistance underscores the urgent need for innovative antimicrobial strategies. This review explores the cutting-edge applications of nanotechnology in combating bacterial infections, addressing a critical healthcare challenge. We critically assess the antimicrobial properties and mechanisms of diverse nanoparticle systems, including liposomes, polymeric micelles, solid lipid nanoparticles, dendrimers, zinc oxide, silver, and gold nanoparticles, as well as nanoencapsulated essential oils. These nanomaterials offer distinct advantages, such as enhanced drug delivery, improved bioavailability, and efficacy against antibiotic-resistant strains. Recent advancements in nanoparticle synthesis, functionalization, and their synergistic interactions with conventional antibiotics are highlighted. The review emphasizes biocompatibility considerations, stressing the need for rigorous safety assessments in nanomaterial applications. By synthesizing current knowledge and identifying emerging trends, this review provides crucial insights for researchers and clinicians aiming to leverage nanotechnology for next-generation antimicrobial therapies. The integration of nanotechnology represents a promising frontier in combating infectious diseases, underscoring the timeliness and imperative of this comprehensive analysis.

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With the rise of antibiotic resistance, the drive to discover novel antimicrobial substances and standard testing methods with the aim of controlling transmissive diseases are substantially high. In healthcare sectors and industries, although methods for testing antibiotics and other aqueous-based reagents are well established, methods for testing nanomaterials, non-polar and other particle-based suspensions are still debatable. Hence, utilities of ISO standard validations of such substances have been recalled where corrective actions had to be taken. This paper reports a serial analysis obtained from testing the antimicrobial activities of 10 metallic-based nanomaterials against 10 different pathogens using five different in vitro assays, where the technique, limitation and robustness of each method were evaluated. To confirm antimicrobial activities of metallic-based nanomaterial suspensions, it was found that at least two methods must be used, one being the agar well diffusion method, which was found to be the most reliable method. The agar well diffusion method provided not only information on antimicrobial efficacy through the size of the inhibitory zones, but it also identified antimicrobial ions and synergistic effects released by the test materials. To ascertain the effective inhibitory concentration of nanoparticles, the resazurin broth dilution method is recommended, as MIC can be determined visually without utilising any equipment. This method also overcomes the limit of detection (LoD) and absorbance interference issues, which are often found in the overexpression of cell debris and nanoparticles or quantum dots with optical profiles. In this study, bimetallic AgCu was found to be the most effective antimicrobial nanoparticle tested against across the bacterial (MIC 7 µg/mL) and fungal (MIC 62.5 µg/mL) species.

The synergistic effects of antimicrobial nanostructures with antibiotics present a promising solution for overcoming resistance in methicillin-resistant Staphylococcus aureus (MRSA). Previous studies have introduced iron as a novel coating for silver nanoparticles (AgNPs) to enhance both economic efficiency and potency against S. aureus. However, there are currently no available data on the potential of these novel nanostructures to reverse MRSA resistance. To address this gap, a population study was conducted within the MRSA community, collecting a total of 48 S. aureus isolates from skin lesions. Among these, 21 isolates (43.75%) exhibited cefoxitin resistance as determined by agar disk diffusion assay. Subsequently, a PCR test confirmed the presence of the mecA gene in 20 isolates, verifying them as MRSA. These results highlight the cefoxitin disk diffusion susceptibility test as an accurate screening method for predicting mecA-mediated resistance in MRSA. Synergy tests were performed on cefoxitin, serving as a marker antibiotic, and iron-coated AgNPs (Fe@AgNPs) in a combination study using the checkerboard assay. The average minimal inhibitory concentration (MIC) and fractional inhibitory concentration (FIC) of cefoxitin were calculated as 11.55 mg/mL and 3.61 mg/mL, respectively. The findings indicated a synergistic effect (FIC index < 0.5) between Fe@AgNPs and cefoxitin against 90% of MRSA infections, while an additive effect (0.5 ≤ FIC index ≤ 1) could be expected in 10% of infections. These results suggest that Fe@AgNPs could serve as an economically viable candidate for co-administration with antibiotics to reverse resistance in MRSA infections within skin lesions. Such findings may pave the way for the development of future treatment strategies against MRSA infections.

Polymethylmethacrylate (PMMA) is the most commonly used bone void filler in orthopedic surgery. However, the biocompatibility and radiopacity of PMMA are insufficient for such applications. In addition to insufficient biocompatibility, the microbial infection of medical implants is one of the frequent causes of failure in bone reconstruction. In the present work, the preparation of a novel PMMA-based hydroxyapatite/ZnFe2O4/ZnO composite with heterophase ZnFe2O4/ZnO NPs as an antimicrobial agent was described. ZnFe2O4/ZnO nanoparticles were produced using the electrical explosion of zinc and iron twisted wires in an oxygen-containing atmosphere. This simple, highly productive, and inexpensive nanoparticle fabrication approach could be readily adapted to different applications. From the findings, the presented composite material showed significant antibacterial activity (more than 99% reduction) against P. aeruginosa, S. aureus, and MRSA, and 100% antifungal activity against C. albicans, as a result of the combined use of both ZnO and ZnFe2O4. The composite showed excellent biocompatibility against the sensitive fibroblast cell line 3T3. The more-than-70% cell viability was observed after 1-3 days incubation of the sample. The developed composite material could be a potential material for the fabrication of 3D-printed implants.

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The urgent need for innovative materials that effectively eliminate bacteria while promoting cell growth to accelerate wound healing has led to the exploration of new options, as current antimicrobial nanoparticles often exhibit high cytotoxicity, which hinders wound closure. In this study, a nano-hybrid composite, named gold-silver-carbon quantum dots (AuAg-CDs), was prepared by embedding gold and silver nanoclusters into carbon dots. The AuAg-CDs nano-hybrid composite demonstrates remarkable biocompatibility, displays potent antibacterial activity, and possesses a unique capability to promote cell proliferation. By physically disrupting bacterial membranes and promoting mammalian cell proliferation, this composite emerges as a highly promising material for wound healing applications. The underlying mechanism of the multifunctional AuAg-CDs was investigated through comprehensive analyses encompassing cell morphology, bacterial membrane potential, levels of reactive oxygen species (ROS), and adenosine triphosphate (ATP) production in both bacterial and mammalian cells. Additionally, AuAg-CDs were incorporated into alginate to create a hydrogel wound dressing, which underwent evaluation using animal models. The results underscore the remarkable potential of the AuAg-CDs wound dressing in facilitating the proliferation of wound fibroblasts and combating bacterial infections. The significance of designing multifunctional nanomaterials to address the challenges associated with pathogenic bacterial infections and regenerative medicine is highlighted by this study, paving the way for future advancements in these fields.

(1) Background: The aim of this research was to investigate the antibacterial activity of dissolved silver from silver-coated titanium implants against Streptococcus mutans. (2) Methodology: Silver-coated titanium implant discs were immersed in 1.8 mL of brain heart infusion broth (BHIB) and incubated for 24 h in order to release the silver ions into the broth. The coating quality was confirmed via EDS, and the dissolved silver was measured via inductively coupled plasma mass spectrometry (ICP-MS). The experimental design used unconditioned broth (control) and broth conditioned with silver released from silver-coated titanium implants (n = 6). Regarding the antibacterial activity, isolated Streptococcus mutans was used. A turbidity test and lactate production test were performed to determine the effect of dissolved silver on bacterial growth in a suspension and biofilm formation. (3) Result: The results showed that the coating was successfully applied on the substrate. There was around 0.3 mg/L of silver released into the BHIB, and the turbidity of the control group was significantly higher than the treatment, with measured absorbance values of 1.4 and 0.8, respectively, indicating that the dissolved silver ions from the silver-coated titanium discs exhibited some degree of antibacterial activity by preventing the growth of Streptococcus mutans. However, the results of the antibiofilm activity test did not show any significant difference between the groups. (4) Conclusion: The dissolved silver from silver-coated titanium implants has an antibacterial activity but not a significant antimicrobial activity, indicating that the dissolved silver from silver-coated titanium abutments can significantly reduce the incidence of peri-implant mucositis.

Polymeric nanoparticles (NPs) present some ideal properties as biomedical nanocarriers for targeted drug delivery such as enhanced translocation through body barriers. Biopolymers, such as polyhydroxyalkanoates (PHAs) are gaining attention as nanocarrier biomaterials due to their inherent biocompatibility, biodegradability, and ability to be vehiculized through hydrophobic media, such as the lung surfactant (LS). Upon colonization of the lung alveoli, below the LS layer, Streptococcus pneumoniae, causes community-acquired pneumonia, a severe respiratory condition. In this work, we convert PHA NPs into an antimicrobial material by the immobilization of an enzybiotic, an antimicrobial enzyme, via a minimal PHA affinity tag. We first produced the fusion protein M711, comprising the minimized PHA affinity tag, MinP, and the enzybiotic Cpl-711, which specifically targets S. pneumoniae. Then, a PHA nanoparticulate suspension with adequate physicochemical properties for pulmonary delivery was formulated, and NPs were decorated with M711. Finally, we assessed the antipneumococcal activity of the nanosystem against planktonic and biofilm forms of S. pneumoniae. The resulting system displayed sustained antimicrobial activity against both, free and sessile cells, confirming that tag-mediated immobilization of enzybiotics on PHAs is a promising platform for bioactive antimicrobial functionalization.

Platinum nanoparticles (PtNPs) are being intensively explored as efficient nanozymes due to their biocompatibility coupled with excellent catalytic activities, which make them potential candidates as antimicrobial agents. Their antibacterial efficacy and the precise mechanism of action are, however, still unclear. In this framework, we investigated the oxidative stress response of Salmonella enterica serovar Typhimurium cells when exposed to 5 nm citrate coated PtNPs. Notably, by performing a systematic investigation that combines the use of a knock-out mutant strain 12023 HpxF- with impaired response to ROS (ΔkatE ΔkatG ΔkatN ΔahpCF ΔtsaA) and its respective wild-type strain, growth experiments in both aerobic and anaerobic conditions, and untargeted metabolomic profiling, we were able to disclose the involved antibacterial mechanisms. Interestingly, PtNPs exerted their biocidal effect mainly through their oxidase-like properties, though with limited antibacterial activity on the wild-type strain at high particle concentrations and significantly stronger action on the mutant strain, especially in aerobic conditions. The untargeted metabolomic analyses of oxidative stress markers revealed that 12023 HpxF- was not able to cope with PtNPs-based oxidative stress as efficiently as the parental strain. The observed oxidase-induced effects comprise bacterial membrane damage as well as lipid, glutathione and DNA oxidation. On the other hand, in the presence of exogenous bactericidal agents such as hydrogen peroxide, PtNPs display a protective ROS scavenging action, due to their efficient peroxidase mimicking activity. This mechanistic study can contribute to clarifying the mechanisms of PtNPs and their potential applications as antimicrobial agents.