Bacterial Biofilm Eradication Research Articles

A polymyxin B loaded hypoxia-responsive liposome with improved biosafety for efficient eradication of bacterial biofilms

A polymyxin B loaded hypoxia-responsive liposome with improved biosafety for efficient eradication of bacterial biofilms

Biotin-modified mesoporous silica nanoparticles as a delivery system for quercetin and gallic acid for bacterial biofilm eradication

The effective management of biofilm-associated infections remains a pressing concern in clinical practice, necessitating the development of efficient eradication strategies. This study introduces biotin-modified mesoporous silica nanoparticles (MSN-Biotin) designed to facilitate the delivery of phytochemical agents, including gallic acid and quercetin, for biofilm disruption. We elucidate the synthesis, characterization, and biofilm penetration ability of MSN-Biotin towards gram-negative E. coli biofilm and gram-positive S. mutans biofilms, emphasizing their potential in anti-biofilm drug delivery. Importantly, in vitro experiments demonstrate that MSN-Biotin loaded with phytochemicals achieved significantly better penetration into E. coli and S. mutans biofilms than traditional mesoporous silica nanoparticles and better biofilm eradication ability than free phytochemical molecules. These findings underscore the promise of MSN-Biotin as a potential efficient platform for delivering antimicrobial agents. This study introduces a novel surface modification approach for the development of antibiofilm nanoparticle systems and establishes their significant potential in biofilm infection management.

Nano-architectonics of Pt single-atoms and differently-sized nanoparticles supported by manganese-oxide nanosheets and impact on catalytic and anti-biofilm activities

Hybrid-nanozymes are promising in various applications, but comprehensive comparison of hybrid-nanozymes composed of single-atoms or nanoparticles on the same support has never been made. Here, manganese-oxide nanosheets were loaded with Pt-single-atoms or differently-sized nanoparticles and their oxidase- and-peroxidase activities compared. High-resolution Transmission-Electron-Microscopy and corresponding Fast Fourier Transform imaging showed that Pt-nanoparticles (1.5 nm diameter) had no clear (111) crystal-planes, while larger nanoparticles had clear (111) crystal-planes. X-ray Photo-electron Spectroscopy demonstrated that unloaded nanosheets were composed of MnO2 with a high number of oxygen vacancies (Vo/Mn 0.4). Loading with 7.0 nm Pt-nanoparticles induced a change to Mn2O3, while loading with 1.5 nm nanoparticles increased the number of vacancies (Vo/Mn 1.2). Nanosheets loaded with 3.0 nm Pt-nanoparticles possessed similarly high catalytic activities as Pt-single-atoms. However, loading with 1.5 nm or 7.0 nm Pt-nanoparticles yielded lower catalytic activities. A model is proposed explaining the low catalytic activity of under- and over-sized Pt-nanoparticles as compared with intermediately-sized (3.0 nm) Pt-nanoparticles and single-atoms. Herewith, catalytic activities of hybrid-nanozymes composed of single-atoms and intermediately-sized nanoparticles are put a par, as confirmed here with respect to bacterial biofilm eradication. This conclusion facilitates a balanced choice between using Pt-single-atoms or nanoparticles in further development and application of hybrid-nanozymes.

Evaluation of the Bacteriophage MAC-1 Potential to Control Pseudomonas aeruginosa Planktonic Cells and Biofilms

Pseudomonas aeruginosa is a pathogenic bacterium that can be considered a high risk to human health due to its remarkable capacity to resist antibiotics, either intrinsically or following the acquisition of resistance genes. P. aeruginosa has been considered a major threat to human health as all the known remedies seem ineffective. Bacteriophages as a natural killer of bacteria can offer alternative therapy for antibiotics. The study aimed to isolate and characterize a lytic bacteriophage against P. aeruginosa (clinically resistant strain/superbug) and to investigate its lytic potential to control bacterial planktonic cells and their biofilms on stainless steel surfaces. A lytic bacteriophage known as MAC-1 was isolated from wastewater against the selected P. aeruginosa-2750 strain. Its host range was moderate and it only infected six isolates. Phage MAC-1 was characterized through transmission electron microscopy and was classified to the Siphoviridae family. It has good heat and pH stability. Its latent time was 24 min with a burst size of about 410 virions per cell. The phage MAC-1 efficacy was determined against P. aeruginosa planktonic cells and biofilms on metallic surfaces. Isolated phage MAC-1 demonstrated promising activity against bacterial planktonic cells as well as in reducing bacterial biofilm biomass formed in 96-well and on stainless steel plates. However, a phage cocktail may be used to avoid resistance and ensure complete eradication of bacterial biofilms.

Microenvironment‐Adaptive Metallo‐Polymeric Nanodecoys via Subcomponent Coordination for Bacterial Biofilm Eradication and Immunomodulation

AbstractBiofilm‐associated infections pose complex challenges that require addressing the multifaceted requirements of biofilm disruption, bacterial killing, and immunomodulation. In this study, microenvironment‐adaptive metallo‐polymeric nanodecoys (MPNs) are synthesized through one‐pot subcomponent coordination in aqueous solution, effectively eradicating bacterial biofilms and modulating immune response. Within the acidic microenvironment of biofilms, the positively charged MPNs demonstrated the ability to interact with and eliminate bacteria while facilitating a Fenton‐like reaction for efficient eradication of bacterial biofilms. As the local microenvironment shifted from a neutral to a basic state during subsequent tissue healing processes, the MPNs adaptively harness the multiple properties to bind pathogen‐associated molecular patterns, scavenge reactive oxygen species, thereby modulating the immune response, alleviating inflammation, and promoting tissue healing. This study presents an efficient strategy for preparing enzyme‐mimicking materials that closely resemble natural metalloenzymes, and the MPNs offer an efficient alternative to current antibiotic treatments for biofilm‐associated infections.

A self‐regulated phototheranostic nanosystem with single wavelength‐triggered energy switching and oxygen supply for multimodal synergistic therapy of bacterial biofilm infections

AbstractThe exploration of antibiotic‐independent phototherapy strategies for the treatment of bacterial biofilm infections has gained significant attention. However, efficient eradication of bacterial biofilms remains a challenge. Herein, a self‐regulated phototheranostic nanosystem with single wavelength‐triggered photothermal therapy (PTT)/photodynamic therapy (PDT) transformation and oxygen supply for multimodal synergistic therapy of bacterial biofilm infections is presented. This approach combines a eutectic mixture of natural phase‐change materials (PCMs) and an aggregation‐induced emission (AIE) phototheranostic agent TPA‐ICN to form colloidally stable nanopartcicles (i.e. AIE@PCM NPs). The reversible solid−liquid phase transition of PCMs facilitates the adaptive regulation of the aggregation states of TPA‐ICN, enabling a switch between the energy dissipation pathways for enhanced PDT in solid PCMs or enhanced PTT in liquid PCMs. Additionally, oxygen‐carrying thermoresponsive nanoparticles are also introduced to alleviate the hypoxic microenvironment of biofilms by releasing oxygen upon heating by AIE@PCM NPs with enhanced PTT. The nanosystem exhibits outstanding therapeutic efficacy against bacterial biofilms both in vitro and in vivo, with an antibacterial efficiency of 99.99%. This study utilizes a self‐regulated theranostic nanoplatform with adaptive PTT/PDT transformation via the phase transition of PCMs and heat‐triggered oxygen release, holding great promise in the safe and efficient treatment of bacterial biofilm infections.

Simultaneous Biofilm Disruption, Bacterial Killing, and Inflammation Elimination for Wound Treatment Using Silver Embellished Polydopamine Nanoplatform.

Due to the presence of spatial barriers, persistent bacteria, and excessive inflammation in bacteria biofilm-infected wounds, current nanoplatforms cannot effectively address these issues simultaneously during the therapeutic process. Herein, a novel biomimetic photothermal nanoplatform integrating silver and polydopamine nanoparticles (Ag/PDAs) that can damage biofilms, kill bacterial persisters, and reduce inflammation for wound treatment is presented. These findings reveal that Ag/PDAs exhibit a broad-spectrum antimicrobial activity through direct damage to the bacterial membrane structure. Additionally, Ag/PDAs demonstrate a potent photothermal conversion efficiency. When combined with near-infrared (NIR) irradiation, Ag/PDAs effectively disrupt the spatial structure of biofilms and synergistically eradicate the resident bacteria. Furthermore, Ag/PDAs show remarkable anti-inflammatory properties in counteracting bacterium-induced macrophage polarization. The in vivo results confirm that the topical application of Ag/PDAs significantly suppress Staphylococcus aureus biofilm-infected wounds in murine models, concurrently facilitating wound healing. This research provides a promising avenue for the eradication of bacterial biofilms and the treatment of biofilm-infected wounds.

In situ generating CO gas for destroying bacterial biofilms

The resistance and impermeability of bacterial biofilms lead to incurable infections. Interference with bacterial respiration is the key to the eradication of bacterial biofilm, but breaking the deep-tissue biofilm barrier to disrupt bacterial respiration still lacks effective means. Here, we report a hydrogel microsphere that disrupts bacterial respiration, supports in situ production of carbon monoxide gas (CO) to enhance the oxygen-depleted environment of biofilms and disrupts the bacterial respiratory chain, eliminating the bacterial biofilm ecotone (BRDMs). Under the specific interaction of α-helical structure and bacterial biofilm, BRDMs rapidly anchored and accumulated on the surface of bacterial biofilm within 8 h. Meanwhile, 8.64 μM CO gas was released in situ under an oxidative stress environment to deeply penetrate the biofilm and continuously destroy bacterial terminal oxidase, block bacterial respiration and finally disintegrate the biofilm. In a model of osteomyelitis, BRDMs disrupt the ecotopic colonization of MRSA biofilms in deep tissues, reduce inflammation, restore internal environmental homeostasis and accelerate tissue regeneration. BRDMs could be designed to remove drug-resistant biofilms from a wide range of deep tissues.

Improved electro-destruction of bacterial biofilms by coating conductive surfaces with polymers

The formation of biofilm involves cell aggregation and adherence, enveloped by a self-produced extracellular matrix. In the medical domain, biofilm-associated infections pose significant challenges, especially concerning implants. This investigation focuses on enhancing electromediated bacterial biofilm eradication through polymer coatings on the anode. These coatings catalyze reactive oxygen species (ROS) generation or convert hydrophobic coatings to bactericidal hydrophilic polycations, detaching the biofilms that are predominantly polyanionic. The first approach employs a metallized polytetrathienylporphyrin layer with ROS catalytic capability, while the second involves an insoluble hydrophobic polyamide, which, upon oxidation, transforms into a bactericidal hydrolytically degradable polycation. Both approaches show promising efficacy in augmenting electromediated Staphylococcus aureus biofilm destruction.

Imidazolium-Based Main-Chain Copolymers With Alternating Sequences for Broad-Spectrum Bactericidal Activity and Eradication of Bacterial Biofilms.

In response to the escalating challenge of bacterial drug resistance, the imperative to counteract planktonic cell proliferation and eliminate entrenched biofilms underscores the necessity for cationic polymeric antibacterials. However, limited efficacy and cytotoxicity challenge their practical use. Here, novel imidazolium-based main-chain copolymers with imidazolium (PIm+) as the cationic component are introduced. By adjusting precursor molecules, hydrophobicity and cationic density of each unit are fine-tuned, resulting in broad-spectrum bactericidal activity against clinically relevant pathogens. PIm+1 stands out for its potent antibacterial performance, with a minimum inhibitory concentration of 32µg mL-1 against Methicillin-resistant Staphylococcus aureus (MRSA), and substantial biofilm reduction in Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) biofilms. The bactericidal mechanism involves disrupting the outer and cytoplasmic membranes, depolarizing the cytoplasmic membrane, and triggering intracellular reactive oxygen species (ROS) generation. Collectively, this study postulates the potential of imidazolium-based main-chain copolymers, systematically tailored in their sequences, to serve as a promising candidate in combatting drug-resistant bacterial infections.

Multi-targeting oligopyridiniums: Rational design for biofilm dispersion and bacterial persister eradication

The development of effective antibacterial drugs to combat bacterial infections, particularly the biofilm-related infections, remains a challenge. There are two important features of bacterial biofilms, which are well-known critical factors causing biofilms hard-to-treat in clinical, including the dense and impermeable extracellular polymeric substances (EPS) and the metabolically repressed dormant and persistent bacterial population embedded. These characteristics largely increase the difficulty for regular antibiotic treatment due to insufficient penetration into EPS. In addition, the dormant bacteria are insensitive to the growth-inhibiting mechanism of traditional antibiotics. Herein, we explore the potential of a series of new oligopyridinium-based oligomers bearing a multi-biomacromolecule targeting function as the potent bacterial biofilm eradication agent. These oligomers were rationally designed to be “charge-on-backbone” that can offer a special alternating amphiphilicity. This novel and unique feature endows high affinity to bacterial membrane lipids, DNAs as well as proteins. Such a broad multi-targeting nature of molecules not only enables its penetration into EPS, but also plays vital roles in the bactericidal mechanism of action that is highly effective against dormant and persistent bacteria. Our in vitro, ex vivo, and in vivo studies demonstrated that OPc3, one of the most effective derivatives, was able to offer excellent antibacterial potency against a variety of bacteria and effectively eliminate biofilms in zebrafish models and mouse wound biofilm infection models.

One-Stop Integrated Nanoagent for Bacterial Biofilm Eradication and Wound Disinfection.

To meet the requirements of biomedical applications in the antibacterial realm, it is of great importance to explore nano-antibiotics for wound disinfection that can prevent the development of drug resistance and possess outstanding biocompatibility. Therefore, we attempted to synthesize an atomically dispersed ion (Fe) on phenolic carbon quantum dots (CQDs) combined with an organic photothermal agent (PTA) (Fe@SAC CQDs/PTA) via a hydrothermal/ultrasound method. Fe@SAC CQDs adequately exerted peroxidase-like activity while the PTA presented excellent photothermal conversion capability, which provided enormous potential in antibacterial applications. Based on our work, Fe@SAC CQDs/PTA exhibited excellent eradication of Escherichia coli (>99% inactivation efficiency) and Staphylococcus aureus (>99% inactivation efficiency) based on synergistic chemodynamic therapy (CDT) and photothermal therapy (PTT). Moreover, in vitro experiments demonstrated that Fe@SAC CQDs/PTA could inhibit microbial growth and promote bacterial biofilm destruction. In vivo experiments suggested that Fe@SAC CQDs/PTA-mediated synergistic CDT and PTT exhibited great promotion to wound disinfection and recovery effects. This work indicated that Fe@SAC CQDs/PTA could serve as a broad-spectrum antimicrobial nano-antibiotic, which was simultaneously beneficial for bacterial biofilm eradication, wound disinfection, and wound healing.

Dual therapy for the eradication of bacterial biofilms: Iron oxide nanoparticles and carbon dots as magnetic actuator and photothermal agents

Nanohybrids based on maghemite iron oxide nanoparticles (IONPs) and carbon dots (CDs), with different linkers between the two components, are synthesized, with the idea of combining several properties (magnetic and optical) in one nanomaterial in order to eradicate bacterial biofilm. The photothermal capacities of these materials are expressed by two parameters: the specific absorption rate (SAR) and the photothermal light-to-heat conversion constant (η). They show that the IONP/CD combination is more effective in photothermia (PT) than either of the components, but depends on the linkage (amide > ester > electrostatic). The antibacterial properties of the nanohybrids are first determined for the exponential and stationary growth phases of planktonic S. aureus and B. subtilis with and without PT. In the absence of PT, no nanohybrid has any significant bactericidal effect, but with PT the nanohybrids have different activities, with the IONP-amide-CD pattern the most effective. Combining magnetic actuation and PT on B. subtilis biofilms shows a synergistic effect and reveals the advantages of using such nanohybrid materials for killing bacteria and eradicating biofilm.

Exploring the antibacterial and dermatitis-mitigating properties of chicken egg white-synthesized zinc oxide nano whiskers.

Zinc oxide nanoparticles (ZnO-NPs) have garnered considerable interest in biomedical research primarily owing to their prospective therapeutic implications in combatting pathogenic diseases and microbial infections. The primary objective of this study was to examine the biosynthesis of zinc oxide nanowhiskers (ZnO-NWs) using chicken egg white (albumin) as a bio-template. Furthermore, this study aimed to explore the potential biomedical applications of ZnO NWs in the context of infectious diseases. The NWs synthesized through biological processes were observed using electron microscopy, which allowed for detailed examination of their characteristics. The results of these investigations indicated that the NWs exhibited a size distribution ranging from approximately 10 to 100 nm. Fourier-transform infrared spectroscopy (FTIR) and scanning electron microscopy-energy dispersive X-ray spectroscopy (SEM-EDX) mapping analyses successfully corroborated the size, dimensions, and presence of biological constituents during their formation. In this study, XTT assay and confocal imaging were employed to provide evidence of the efficacy of ZnO-NWs in the eradication of bacterial biofilms. The target bacterial strains were Staphylococcus aureus and Escherichia coli. Furthermore, we sought to address pertinent concerns regarding the biocompatibility of the ZnO-NWs. This was achieved through comprehensive evaluation of the absence of cytotoxicity in normal HEK-293T and erythrocytes. The findings of this investigation unequivocally confirmed the biocompatibility of the ZnO-NWs. The biosynthesized ZnO-NWs demonstrated a noteworthy capacity to mitigate the dermatitis-induced consequences induced by Staphylococcus aureus in murine models after a therapeutic intervention lasting for one week. This study presents a comprehensive examination of the biosynthesis of zinc oxide nanowhiskers (ZnO-NWs) derived from chicken egg whites. These findings highlight the considerable potential of biosynthesized ZnO-NWs as a viable option for the development of therapeutic agents targeting infectious diseases. The antibacterial efficacy of ZnO-NWs against both susceptible and antibiotic-resistant bacterial strains, as well as their ability to eradicate biofilms, suggests their promising role in combating infectious diseases. Furthermore, the confirmed biocompatibility of ZnO-NWs opens avenues for their safe use in biomedical applications. Overall, this research underscores the therapeutic promise of ZnO-NWs and their potential significance in future biomedical advancements.

A global bibliometric and visualized analysis of bacterial biofilm eradication from 2012 to 2022

BackgroundTo deeply explore the dynamic trends, focal points and emerging topics of bacterial biofilm eradication field and provide novel insights for prospective research endeavors, the first global bibliometric and visualized analysis of the field was employed in this study.MethodsThe study meticulously curated articles and reviews concentrating on biofilm eradication from the Web of Science Core Collection (WoSCC) and identified literature published in 2012–2022 for further analysis, and the bibliometric and visualized analysis was performed to elucidate a clustering pattern in the domain with tools mainly including CiteSpace and VOSviewer.Results15,503 authors affiliated with 2,397 institutions spanning 96 countries or regions contributed to a corpus of 3,201 articles, containing 7,005 keywords. The USA emerged as a commanding vanguard in exploring the antibiofilm strategies and displaying pioneering initiatives within this sphere. The Chinese Academy of Sciences (CAS) emerged as the most prolific source of publications. Noteworthy among authors, Pandian Shunmugiah Karutha secured the lead in article contributions as well as co-citations while Deng Le with his team is poised to become a dominant influence in the future. Despite that, the extent of collaborative engagement across different institutions and authors appeared to fall short of its potential. Frontiers in Microbiology led the discourse by publishing a substantial body of articles and standing as the most recurrently co-cited publication. The most influential research domains encompassed “bacterial biofilm formation, “photodynamic therapy” and “phage therapy.” Recent trends and forefronts concentrate on intensifying research into facilitating the shift of multiple strategies for biofilm eradication from controlled lab settings or animal studies to real-world clinical environments.ConclusionFundamentally, this study presents a comprehensive scrutiny and reveals that the realm of bacterial biofilm eradication is undergoing rapid evolution, with even greater expansion anticipated in the times ahead. Subsequent scholars should emphasize the augmentation of collaborative efforts and focus their energies on emerging topics, thus contributing to break through current barriers in transitioning biofilm eradication strategies from the “fundamental” stage to “practical” application.

K6[P2Mo18O62] as DNase-Mimetic Artificial Nucleases to Promote Extracellular Deoxyribonucleic Acid Degradation in Bacterial Biofilms.

In the current study, the DNase-like activity of the Dawson-type polyoxometalate K6[P2Mo18O62] was explored. The obtained findings demonstrated that K6[P2Mo18O62] could effectively cleave phosphoester bonds in the DNA model substrate (4-nitrophenyl phosphate) and result in the degradation of plasmid DNA. Moreover, the application potential of this Dawson-type polyoxometalate as a DNase-mimetic artificial enzyme to degrade extracellular DNA (eDNA) in Escherichia coli (E. coli) bacterial biofilm was explored. The results demonstrated that K6[P2Mo18O62] exhibited high cleavage ability toward eDNA secreted by E. coli and thus eradicated the bacterial biofilm. In conclusion, Dawson-type polyoxometalate K6[P2Mo18O62] possessed desirable DNase-like activity, which could serve as a bacterial biofilm eradication agent by cleaving and degrading eDNA molecules.

A near-infrared light-triggered nano-domino system for efficient biofilm eradication: Activation of dispersing and killing functions by generating nitric oxide and peroxynitrite via cascade reactions

One of the serious threats to global public health is the bacterial biofilm, which results in numerous persistent and recurrent infections. Herein, we proposed a near-infrared (NIR) light-triggered “nano-domino” system with “dispersing and killing” functionality for biofilm eradication. The nanoplatform was fabricated by the self-assembly of chitosan conjugated with L-arginine (L-Arg, a natural nitric oxide (NO) donor) and indocyanine green (ICG, a phototherapy agent). Using an NIR irradiation “trigger”, a series of reactive oxygen species (ROS) including singlet oxygen (1O2), hydrogen peroxide (H2O2), and superoxide anions (·O2−), as well as heat were generated from ICG aggregates. Subsequently, 1O2 and H2O2 catalyzed L-Arg to produce NO, which dispersed the biofilm and reacted with ·O2− to form peroxynitrite to kill bacteria with ROS collaboratively. Meanwhile, the generated heat increased the permeability of bacterial membranes, aggravating the damage to biofilm bacteria. The experiments on biofilm eradication demonstrated that this “nano-domino” system was capable to eradicate over 99.99% of biofilms formed by Methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa under 5-min NIR irradiation. Notably, these integrated benefits allowed the system to promote the healing of MRSA biofilm-infected wounds in vivo with negligible toxicity. Overall, this reported NIR-triggered “nano-domino” system holds great promise for addressing the difficulties associated with bacterial biofilm eradication. Statement of significanceNovel agents for biofilm eradication are urgently needed due to the alarming rise in antimicrobial resistance to conventional antibiotics and the critical shortage of new drugs. In this study, we created a nano-domino system that uses near-infrared (NIR) light as a trigger to eradicate mature biofilms. In response to a short-term NIR irradiation, the proposed nanoplatform could generate nitric oxide and peroxynitrite to disperse the biofilm and kill the bacteria inside, respectively, leading to efficient eradication of Methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa biofilms with minimal cytotoxicity. The findings, therefore, indicate that this nanoplatform with enhanced antibiofilm performance might provide a reliable and promising solution to biofilm-related problems.

The Potential Effects of the Essential Oil of Coriander Seeds on Bacterial Biofilm and Immune Cells

Background: Nowadays, the pharmacological activities of many natural phytochemicals have a huge impact on pharmaceutical research and drug development. Hence, numerous studies have been conducted to investigate plants' efficacy, fractions, and isolated pure compounds to discover new therapeutic agents. Aim: This study aimed to evaluate the potential activity of coriander essential oil (CEO) on bacterial biofilm and immune cells. Methods: CEO has been extracted from the seeds through the hydrodistillation method, and its chemical composition was analyzed using gas chromatography (GC) and Nuclear magnetic resonance (NMR). The antibacterial activity of CEO was assessed using different bacterial strains (P. aeruginosa, S. aureus, S. epidermidis and E. coli), both in planktonic and biofilm forms. In addition, this activity has been investigated individually and in combination with selected antibiotics (Gentamicin and Ciprofloxacin), using the bacterial enumeration following the MBEC Assay® protocol. Pyocianin (PYO) has been measured using a plate reader on 690 nm absorbance, where wells tested were treated with different CEO concentrations (12.5, 25, 50 and 100 mg/mL). An MTT assay was also used to examine the CEO'seffect on the viability of RAW 246.7 murine macrophages. Data were analyzed using GraphPad Prism 9 software. Results: Six major compounds were identified in CEO; Linalool was the most predominant. Regarding the activity of the CEO on planktonic bacteria, cell count was obtained and calculated as log reductions; significant log reductions (p<0.05) were measured on 300 mg/mL of CEO for all P. aeruginosa, S. aureus, S. epidermidis and E. coli, 2.00, 6.73, 6.93 and 7.68 respectively. While for the bacterial biofilm, a significant (p<0.05) log reduction in the cell count was obtained at 300 mg/mL of CEO for all of P. aeruginosa, S. aureus, S. epidermidis and E. coli, 2.22, 5.33, 5.83 and 6.76, respectively. Minimum inhibitory concentrations (MIC) of the combination of antibiotics Gentamicin (0.60, 0.15, 1.22, 0.3 µg/mL) or Ciprofloxacin (0.075, 0.03, 0.004 and 0.002 µg/mL) for all P. aeruginosa, S. aureus, S. epidermidis and E. coli, respectively, with 50 mg/mL of CEO on planktonic and biofilm bacteria. PYO measurements obtained showed anti-quorum sensing activity of CEO, the absorbance detecting PYO levels, was decreasing as the concentration of CEO was increasing, absorbances were (0.66, 0.075, 0.097 and 0.11), whereas the control of P. aeruginosa was (0.124). On the other hand, the antibacterial/antibiofilm concentrations were cytotoxic (percentage of viability <80%) to macrophages and the safe level was (0.30 mg/mL) of CEO. Conclusion: These results indicated that CEO may have a promising role in bacterial biofilm eradication, which may help manage and prevent chronic infections in the future. However, more investigations are required to understand the exact mechanism and improve its safety on immune cells.

A nanoplatform with oxygen self-supplying and heat-sensitizing capabilities enhances the efficacy of photodynamic therapy in eradicating multidrug-resistant biofilms

Bacterial biofilms, especially those caused by multidrug-resistant bacteria, have emerged as one of the greatest dangers to global public health. The acceleration of antimicrobial resistance to conventional antibiotics and the severe lack of new drugs necessitates the development of novel agents for biofilm eradication. Photodynamic therapy (PDT) is a promising non-antibiotic method for treating bacterial infections. However, its application in biofilm eradication is hampered by the hypoxic microenvironment of biofilms and the physical protection of extracellular polymeric substances. In this study, we develop a composite nanoplatform with oxygen (O2) self-supplying and heat-sensitizing capabilities to improve the PDT efficacy against biofilms. CaO2/ICG@PDA nanoparticles (CIP NPs) are fabricated by combining calcium peroxide (CaO2) with the photosensitizer indocyanine green (ICG) via electrostatic interactions, followed by coating with polydopamine (PDA). The CIP NPs can gradually generate O2 in response to the acidic microenvironment of the biofilm, thereby alleviating its hypoxic state. Under near-infrared (NIR) irradiation, the nanoplatform converts O2 into a significant amount of singlet oxygen (1O2) and heat to eradicate biofilm. The generated heat enhances the release of O2, accelerates the generation of 1O2 in PDT, increases cell membrane permeability, and increases bacterial sensitivity to 1O2. This nanoplatform significantly improves the efficacy of PDT in eradicating biofilm-dwelling bacteria without fostering drug resistance. Experiments on biofilm eradication demonstrate that this nanoplatform can eradicate over 99.9999% of methicillin-resistant Staphylococcus aureus (MRSA) biofilms under 5-min NIR irradiation. Notably, these integrated advantages enable the system to promote the healing of MRSA biofilm-infected wounds with negligible toxicity in vivo, indicating great promise for overcoming the obstacles associated with bacterial biofilm eradication.

Precise Molecular Engineering of Type I Photosensitizer with Aggregation-Induced Emission for Image-Guided Photodynamic Eradication of Biofilm.

Biofilm-associated infections exert more severe and harmful attacks on human health since they can accelerate the generation and development of the antibiotic resistance of the embedded bacteria. Anti-biofilm materials and techniques that can eliminate biofilms effectively are in urgent demand. Therefore, we designed a type I photosensitizer (TTTDM) with an aggregation-induced emission (AIE) property and used F-127 to encapsulate the TTTDM into nanoparticles (F-127 AIE NPs). The NPs exhibit highly efficient ROS generation by enhancing intramolecular D-A interaction and confining molecular non-radiative transitions. Furthermore, the NPs can sufficiently penetrate the biofilm matrix and then detect and eliminate mature bacterial biofilms upon white light irradiation. This strategy holds great promise for the rapid detection and eradication of bacterial biofilms.