•The spread of resistant bacteria and the development bacterial biofilm have been two major challenges.•Biofilm infections are notoriously difficult to treat, as the matrix provides physical ...protection.•Phototherapy including photothermal therapy and photodynamic therapy has attracted wide attentions.•This review describes the latest phototherapy strategies to resist resistant bacteria and biofilms infections.
The spread of resistant bacteria and the development bacterial biofilm have been two major challenges in the application of biomaterials, causing device failure as well as tissue infections. The overuse of antibiotics has become a common cause of the emergence of multiple antibiotics-resistant bacteria. Besides, biofilm infections are notoriously difficult to treat, as the biofilm matrix provides physical protection from antibiotic treatment. Recently, nanomaterials with high drug loading capacity, various types of stimuli responsiveness, smart targeting and small-size are able to increase local drug concentration and to escape the capture of macrophages. Especially, the loading of drugs to the nanomaterials enhances chances for macrophage capture which is a serious problem related to interaction with immune system. Phototherapy including photothermal therapy and photodynamic therapy has attracted wide attentions in treating infectious diseases as the development of drug-resistant bacteria and bacterial biofilms. In addition, based on the special microenvironment of bacterial infections, various construction and modification methods of nanomaterials showed high efficient antibacterial properties. This review describes the latest advances in the phototherapy strategies to resist resistant bacteria and biofilms related infections.
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•MAPC as a novel biofilm microenvironment-responsive nanoplatform can decompose in the acidic biofilm microenvironment and subsequently releases the α-amylase, manganese oxide and ...sonosensitizer.•MAPC released α-amylase can selectively degrade the extracellular polymeric substances of MRSA biofilms and further promotes the sonosensitizer penetration.•MAPC released manganese oxide with catalase-like activity can convert the overproduced H2O2 into O2 to relieve the hypoxic biofilm microenvironment, which significantly enhances the sonodynamic antimicrobial efficiency.•MAPC offers an effective therapeutic strategy for superior MRSA biofilm eradication efficiency of combining biofilm structure degradation with improved ultrasound-driven antimicrobial sonodynamic therapy by hypoxia relief.
Treatment of bacterial biofilms remains a great challenge in the clinic. Recently, ultrasound (US)-driven antimicrobial sonodynamic therapy (aSDT) has been considered as an emerging therapeutic strategy for the treatment of biofilm infections. However, the hypoxic microenvironment and restricted diffusion of sonosensitizers within biofilms substantially reduce the therapeutic efficacy of aSDT. Herein, a biofilm microenvironment-responsive nanoplatform was proposed to promote biofilm degradation and sonosensitizer penetration, and relieve the hypoxic microenvironment, thereby augmenting aSDT efficiency against bacterial biofilm infections. This nanoplatform was prepared by modifying manganese dioxide nanosheets (MNS) with α-amylase, polyethylene glycol (PEG), and chlorin e6 (Ce6) to form MNS-α-amylase/PEG-Ce6 nanosheets (MAPC). After delivery into biofilm-infected tissues, MAPC decompose in the acidic biofilm microenvironment to locally release α-amylase and Ce6. The α-amylase degrades the extracellular polymeric substances of biofilms to promote Ce6 penetration. In addition, the MNS catalyze the conversion of endogenously overproduced H2O2 into O2 in infected tissue and relieve the hypoxic microenvironment to further enhance antibiofilm efficacy of aSDT. Such biofilm degradation and hypoxia-relief enhanced aSDT show approximately 6.9 log units (99.99998%) reduction of bacteria within biofilms in vitro, and efficiently treat methicillin-resistant Staphylococcus aureus (MRSA) biofilms-infected mice. Overall, biofilm degradation improves sonosensitizer penetration and relieves the hypoxic biofilm microenvironment to enhance the effects of aSDT by MAPC. Thus, the use of this nanoplatform provides a promising strategy for combating bacterial biofilm-associated infections.
The great clinical significance of biofilm-associated infections and their inherent recalcitrance to antibiotic treatment urgently demand the development of novel antibiofilm strategies. In this ...regard, antimicrobial peptides (AMPs) are increasingly recognized as a promising template for the development of antibiofilm drugs. Indeed, owing to their main mechanism of action, which relies on the permeabilization of bacterial membranes, AMPs exhibit a strong antimicrobial activity also against multidrug-resistant bacteria and slow-growing or dormant biofilm-forming cells and are less prone to induce resistance compared to current antibiotics. Furthermore, the antimicrobial potency of AMPs can be highly increased by combining them with conventional (antibiotics) as well as unconventional bioactive molecules. Combination treatments appear particularly attractive in the case of biofilms since the heterogeneous nature of these microbial communities requires to target cells in different metabolic states (e.g., actively growing cells, dormant cells) and environmental conditions (e.g., acidic pH, lack of oxygen or nutrients). Therefore, the combination of different bioactive molecules acting against distinct biofilm components has the potential to facilitate biofilm control and/or eradication. The aim of this review is to highlight the most promising combination strategies developed so far to enhance the therapeutic potential of AMPs against bacterial biofilms. The rationale behind and beneficial outcomes of using AMPs in combination with conventional antibiotics, compounds capable of disaggregating the extracellular matrix, inhibitors of signaling pathways involved in biofilm formation (i.e., quorum sensing), and other peptide-based molecules will be presented and discussed.
Antimicrobial phototherapy has gained recognition as a promising approach for addressing bacterial biofilms, however, its effectiveness is often impeded by the robust physical and chemical defenses ...of the biofilms. Traditional antibacterial nanoplatforms face challenges in breaching the extracellular polymeric substances (EPS) barrier to efficiently deliver photosensitizers deep into biofilms. Moreover, the prevalent hypoxia within biofilms restricts the success of oxygen-reliant phototherapy. In this study, we engineered a soft mesoporous organosilica nanoplatform (SMONs) by incorporating polyethylene glycol (PEG), catalase (CAT), and indocyanine green (ICG), forming SMONs-PEG-CAT-ICG (SPCI). We compared the antimicrobial efficacy of SPCI with more rigid nanoplatforms. Our results demonstrate that SPCI's unique flexible mechanical properties enable it to navigate through biofilm barriers, markedly enhancing ICG penetration in methicillin-resistant Staphylococcus aureus (MRSA) biofilms. Notably, in a murine subcutaneous MRSA biofilm infection model, SPCI showed superior biofilm penetration and pharmacokinetic benefits over its rigid counterparts. The embedded catalase in SPCI effectively converts excess H2O2 present in infected tissues into O2, alleviating hypoxia and significantly boosting the antibacterial performance of phototherapy. Both in vitro and in vivo experiments confirm that SPCI surpasses traditional rigid nanoplatforms in overcoming biofilm barriers, offering improved treatment outcomes for infections associated with bacterial biofilms. This study presents a viable strategy for managing bacterial biofilm-induced diseases by leveraging the unique attributes of a soft mesoporous organosilica-based nanoplatform.
This research introduces an innovative antimicrobial phototherapy soft nanoplatform that overcomes the inherent limitations posed by the protective barriers of bacterial biofilms. By soft nanoplatform with flexible mechanical properties, we enhance the penetration and delivery of photosensitizers into biofilms. The inclusion of catalase within this soft nanoplatform addresses the hypoxia in biofilms by converting hydrogen peroxide into oxygen in infected tissues, thereby amplifying the antibacterial effectiveness of phototherapy. Compared to traditional rigid nanoplatforms, this flexible nanoplatform not only promotes the delivery of therapeutic agents but also sets a new direction for treating bacterial biofilm infections, offering significant implications for future antimicrobial therapies.
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Bacterial biofilm represents a protected mode of bacterial growth that significantly enhances the resistance to antibiotics. Poly lactic-co-glycolic acid (PLGA)-based nanoparticle ...delivery systems have been intensively investigated to combat the bacterial biofilms-associated infections. However, some drawbacks associated with current PLGA-based nanoformulations (e.g. the relatively low drug loading capability, premature burst release and/or incapability of on-demand release of cargos at the site of action) restrict the transition from the lab research to the clinical applications. One potent strategy to overcome the above-mentioned limitations is exploiting the unique properties of carbon quantum dots (CQDs) and combining CQDs with the conventional PLGA nanoparticles. In the present study, the CQDs were innovatively incorporated into PLGA nanoparticles by using a microfluidic method. The resulting CQD-PLGA hybrid nanoparticles presented good loading capability of azithromycin (a macrolide antibiotic, AZI) and tobramycin (an aminoglycoside antibiotic, TOB), and stimuli-responsive release of the cargos upon laser irradiation. Consequently, AZI-loaded CQD-PLGA hybrid nanoparticles showed chemo-photothermally synergistic anti-biofilm effects against P. aeruginosa biofilms. Additionally, the CQD-PLGA hybrid nanoparticles demonstrated good biocompatibility with the eukaryotic cells. Overall, the proof-of-concept of CQD-PLGA hybrid nanoparticles may open a new possibility in chemo-photothermal therapy against bacterial biofilms.
•Au-TNT generates O2 while releasing ROS under the action of ultrasound.•SDT-mediated Au-TNT has a killing effect on oral multi-species biofilm.•The SDT in a rat peri-implantitis model improves ...bacterial-induced inflammation.•Au-TNT has excellent physicochemical stability for further clinical application.
Peri-implant infection caused by bacterial biofilm is the main reason for dental implant repair failure. The success of controlling infection depends mainly on eliminating bacterial biofilm. However, traditional medicine therapy is not practical due to the growth of bacterial resistance. Recently, antibacterial sonodynamic therapy (aSDT) activated by ultrasound has been recognized as an emerging strategy for treating biofilm infections. In this study, an activatable nanoplatform (Au-TNT) fabricated on the implant surface is proposed for aSDT. Au-TNT could rapidly produce O2 under ultrasonic irradiation, which could relieve the hypoxic microenvironment of biofilm and improve the anti-biofilm efficiency of aSDT. Furthermore, it could generate singlet oxygen (1O2) and hydroxyl radicals (OH), resulting in a powerfully high antibacterial capacity for both single and multi-species pathogenic biofilms as assessed by bacterial survival rate, cell membrane rupture, biofilm metabolism and thickness. Meanwhile, Au-TNT exhibited excellent antibacterial ability in vivo with a 3 logs CFU decreased compared to the control group. Interestingly, it also showed that Au-TNT downregulated inflammatory factor levels and promoted bone repair. Thus, this study provides a sonodynamic-catalytic nanoplatform for efficient biofilm eradication and peri-implant infection treatment.
Central-line-associated bloodstream infections are increasingly recognized to be associated with intraluminal microbial biofilms, and effective measures for the prevention and treatment of ...bloodstream infections remain lacking. This report evaluates a new commercially developed antimicrobial catheter lock solution (ACL), containing trimethoprim (5 mg/ml), ethanol (25%), and calcium EDTA (Ca-EDTA) (3%), for activity against bacterial and fungal biofilms, using
and
(rabbit) catheter biofilm models. Biofilms were formed by bacterial (seven different species, including vancomycin-resistant
VRE) or fungal (
) species on catheter materials. Biofilm formation was evaluated by quantitative culture (CFU) and scanning electron microscopy (SEM). Treatment with ACL inhibited the growth of adhesion-phase biofilms
after 60 min (VRE) or 15 min (all others), while mature biofilms were completely inhibited after exposure for 2 or 4 h, compared to control. Similar results were observed for drug-resistant bacteria. Compared to the heparinized saline controls, ACL lock therapy significantly reduced the catheter bacterial (3.49 ± 0.75 versus 0.03 ± 0.06 log CFU/catheter;
= 0.016) and fungal (2.48 ± 1.60 versus 0.55 ± 1.19 log CFU/catheter segment;
= 0.013) burdens in the catheterized rabbit model. SEM also demonstrated eradication of bacterial and fungal biofilms
on catheters exposed to ACL, while vigorous biofilms were observed on untreated control catheters. Our results demonstrated that ACL was efficacious against both adhesion-phase and mature biofilms formed by bacteria and fungi
and
.
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