Effects of Sonophotodynamic Therapy mediated by Curcumin on adhesion and biofilm formation of Staphylococcus aureus.

Staphylococcus aureus is a relevant gram-positive commensal bacteria of the human body that is responsible to cause from superficial to deep infections. S. aureus has powerful tools that helps the bacteria to invade, establish and cause the infection successfully, such as the adhesion and biofilm formation abilities. Biofilm is a complex microbial organization, where microorganisms are embebbed in a self-produced extra-celular matrix that protects them from chemical agents, physical stress and antimicrobial therapies. The biofilm formation is an endless process which starts with the adhesion of the microorganism to the surface. The need to develop treatments to combat microbial biofilms is unquestionable. In this context, Antimicrobial Photodynamic (PDT), Sonodynamic (SDT) and Sonophotodynamic (SPDT) Therapies are alternative treatments that have been studied worldwide. These therapies are based on the application of a sensitizer, followed by the application of light (PDT), ultrasound (SDT) or both sources (SPDT), to produce reactive species that are lethal to microorganisms, even in the biofilm living form.Previously, we proved that PDT, SDT and SPDT mediated by Curcumin (Cur) were effective to inactivate S. aureus biofilm, and SPDT reached the highest reduction in the viability [1]. The present work evaluated the effects of these therapies on adhesion and biofilm formation abilities of the bacteria S. aureus. For this, biofilms were submitted to sub-lethal doses of SDT, PDT or SPDT and the effects of these treatments were evaluated in the remaining bacteria. First, biofilms were incubated for 20 min with 40 μM of Cur. In SDT group, the ultrasound (US) was applied at 1 MHz, power density of 3 W/cm², 20% of duty cycle and pulse frequency of 100 Hz. For PDT, a blue LED light at the dose of 35 J/cm² was used. The SPDT group received both sources simultaneously using the same parameters as described. Control biofilms were treated with Cur, US or LED light only, or no treatment. The effects immediately after treatments were evaluated by the quantification of colonies (CFU/mL), cell metabolism (XTT assay) and total biomass (crystal violet). For the evaluation of the adhesion and biofilm formation capacities, additional biofilms that received the same treatments were analyzed. The adhesion was assessed by viability assay (CFU/mL), and biofilm-forming ability by CFU/mL and total biomass.Immediately after treatments, SPDT achieved higher reductions in bacteria viability and biomass than PDT and SDT. All treatments reduced the adhesion ability of the bacteria and it is probably related with the metabolism cell reduction observed in the treated groups. Regarding to the biofilm formation ability, the treatments did not reduce the CFU/mL values of the biofilm formed by those cells that survived to the treatments, however, the crystal violet test showed that biofilms exhibited lower biomass, indicating that PDT, SDT and SPDT altered the characteristics of the biofilm morphology. In conclusion, all treatments had the same impact in the adhesion and biofilm formation capacities, turning the biofilm less virulent.     

Efficacy of the combination of P5 peptide and photodynamic therapy mediated by bixin and chlorin-e6 against Cutibacterium acnes biofilm

In this study, the action of antimicrobial peptide (AMP) P5 and antimicrobial photodynamic therapy (aPDT) mediated by bixin and chlorin-e6 (Ce6) on Cutibacterium acnes (C. acnes) in planktonic phase and biofilm were evaluated both as monotherapies and combined therapies. Microbial viability after treatments were quantified by colony-forming units per milliliter of the sample (CFU/mL) and have demonstrated that all treatments employed exerted bactericidal activity, reducing the microbial load by more than 3 log₁₀ CFU/mL, also demonstrating for the first time in the literature the antimicrobial photodynamic effect of bixin that occurs mostly through type I mechanism which was proved by the quantification of superoxide anion production. Bacterial biofilm was completely eliminated only after its exposure to aPDT mediated by this PS, however, Ce6 proved to be a more efficient PS, considering that most of the photodynamic effect of bixin- aPDT was exerted by excitation of the endogenous C porphyrins of C. acnes with blue light. The combination of P5 with Ce6-aPDT showed a synergistic effect on the bacterial biofilm with a reduction in microbial load by more than 10 log₁₀ CFU/mL, in which the ability of P5 to permeabilize the polymeric extracellular matrix of the biofilm explains the obtained results, with greater internalization of the PS as shown by the Confocal Laser Scanning Microscopy. One-way ANOVA (Analysis of Variance) with Tukey's post-test and two-way ANOVA with Bonferroni's post-test were used to compare the values of continuous variables between the control group and the treatment groups.     

Improving antimicrobial activity against endodontic biofilm after exposure to blue light-activated novel curcumin nanoparticle

New therapies involving natural products and nanobiotechnology open additional perspectives to reduce endodontic infections. Curcumin is a natural polyphenol extracted from the dry rhizome of curcuma long Linn with therapeutic properties for application in nanobiotechnology and as a photosensitizer for photodynamic therapy. This study aimed to synthesize a novel polymeric nanoparticle of poly (lactic-co-glycolic acid) (PLGA) loaded with curcumin (NP+Cur), and evaluate its antimicrobial activity against endodontic biofilms. Additionally, its biocompatibility using oral keratinocytes was assessed. The polymeric NP+Cur was prepared by the nanoprecipitation method. Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were calculated for the three endodontic bacteria (Enterococcus faecalis, Streptococcus oralis and Actinomyces viscosus). Antibacterial activity of NP+Cur against single- and multispecies biofilm pre-formed on the botton 24-well plate and into dentin tubules of bovine teeth were evaluated by colony forming units and confocal laser scanning microscopy. The pre-irradiation time was 5 min followed by exposure to blue light-emitting diode at 450 nm for the photodynamic treatment. Cell viability using oral keratinocytes was assessed by Alamar Blue assay. MIC and MBC showed antibacterial activity of NP+Cur against endodontic bacteria. A treatment of pre-formed biofilms of endodontic bacteria with NP+Cur also significantly decreased bacterial viability. The concentration of 325 μg/mL of photoactivated NP+Cur was the one that most reduced the viability of the endodontic bacteria evaluated. Regarding biocompatibility, NP+Cur 325 μg/mL and pure nanoparticles showed a cell viability greater than 80%. The novel polymeric nanoparticles loaded with curcumin may be a promising adjunct use to treatment of endodontic infections.     

Photoantimicrobial activity of Schiff-base morpholino phthalocyanines against drug resistant micro-organisms in their planktonic and biofilm forms

Antimicrobial photodynamic inactivation (aPDI) is a treatment for the eradication of drug-resistant micro-organisms. One of the advantages of this technique, is that there is minimal possibility of microbial resistance. Hence, herein, the preparation and characterization of novel neutral and cationic morpholine containing Schiff base phthalocyanines are reported. The cationic complexes gave moderate singlet oxygen quantum yields (Φ_Δ) of ∼0.2 in aqueous media. Conversely, the neutral complexes generated very low Φ_Δ values making them very poor candidates for antimicrobial studies. The cationic phthalocyanines showed excellent photodynamic activity against planktonic cells of all micro-organisms (Candida albicans, Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus, Salmonella enterica subspecies enterica serovar Choleraesuis, vancomycin-resistant Enterococcus faecium, and methicillin-resistant Staphylococcus aureus). The efficiency of aPDI was shown to be both concentration and light-dose-dependent. Mono biofilms were susceptible when treated with 200 µM of cationic Pcs at 108 J/cm². However, ∼10% of the mixed biofilm survived after treatment.     

Photodynamic therapry with curcumin in the reduction of enterococcus faecalis biofilm in bone cavity: rMicrobiological and spectral fluorescense analysis

BackgroundAntimicrobial photodynamic therapy (PDT) has emerged as a therapeutic strategy to conventional procedures using antibiotics.ObjectiveTo evaluate the antimicrobial effectiveness of PDT using blue light emitting diode (LED) associated with curcumin on biofilms of Enterococcus faecalis in bovine bone cavities and also to analyze the presence of these biofilms through spectral fluorescence.Materials and methodsStandardized suspensions of E. faecalis (ATCC 29212) were incubated in artificial bone cavities for 14 days at 36 °C ± 1 °C for biofilm formation. The test specimens were distributed among the four experimental groups (n = 10): L-C- (control), L + C- (LED for 5 min), L-C+ (curcumin for 5 min) and L + C+ (PDT). Aliquots were collected from the bone cavities after treatments and seeded on BHI agar for 24 h at 36 °C ± 1 °C for CFU count. Before and after each treatment the specimens were submitted to spectral fluorescence, whose images were compared in the Image J program. The log10 CFU/mL results were submitted to the Kruskal–Wallis test (5%) and the biofilm fluorescence spectroscopy results were submitted to the Wilcoxon test (5%).ResultsAll treatments presented statistical difference when compared to the control, and PDT was responsible for the largest reduction (1.92 log10 CFU/mL). There was a reduction in the fluorescence emitted after the treatments, with greater statistical difference in the PDT group.ConclusionPDT was efficient in the reduction of E. faecalis biofilms. In all groups post treatment there was a significant reduction of biofilms in the fluorescence spectroscopy images with greater reduction in the PDT group.     

A comparison of antibacterial and antibiofilm efficacy of phenothiazinium dyes between Gram positive and Gram negative bacterial biofilm

BackgroundAntimicrobial photodynamic therapy (APDT) is a process that generates reactive oxygen species (ROS) in presence of photosensitizer, visible light and oxygen which destroys the bacterial cells. We investigated the photoinactivation efficiency of phenothiazinium dyes and the effect of ROS generation on Gram positive and Gram negative bacterial cell as well as on biofilm.Material and methodsEnterococcus faecalis and Klebsiella pneumonia were incubated with all the three phenothiazinium dyes and exposed to 630 nm of light. After PDT, colony forming unit (CFU) were performed to estimate the cell survival fraction. Intracellular reactive oxygen species (ROS) was detected by DCFH-DA. Crystal violet (CV) assay and extracellular polysaccharides (EPS) reduction assay were performed to analyze antibiofilm effect. Confocal laser electron microscope (CLSM) scanning electron microscope (SEM) was performed to assess the disruption of biofilm.Results8log₁₀ reduction in bacterial count was observed in Enterococcus faecalis while 3log₁₀ in Klebsiella pneumoniae. CV and EPS reduction assay revealed that photodynamic inhibition was more pronounced in Enterococcus faecalis. In addition to this CLSM and SEM study showed an increase in cell permeability of propidium iodide and leakage of cellular constituents in treated preformed biofilm which reflects the antibiofilm action of photodynamic therapy.ConclusionWe conclude that Gram-positive bacteria (Enterococcus faecalis) are more susceptible to APDT due to increased level of ROS generation inside the cell, higher photosensitizer binding efficiency and DNA degradation. Phenothiazinium dyes are proved to be highly efficient against both planktonic and biofilm state of cells.     

Toluidine blue O-induced photoinactivation inhibit the biofilm formation of methicillin-resistant Staphylococcus aureus

BackgroundMethicillin-resistant Staphylococcus aureus (MRSA) is resistant to conventional antimicrobial therapies, allowing for high morbidity and mortality. Photodynamic antimicrobial chemotherapy (PACT) is one method that combines visible harmless light with the optimum wavelength with photosensitizers or dyes, producing singlet oxygen (¹O₂) and reactive oxygen strains (ROS), making permanent damages to the target cells. The purpose of this research is to evaluate the suppression efficacy of toluidine blue O (TBO)-mediated PACT on mature MRSA biofilm in vitro.MethodsIn this study, the 48 h mature biofilm of the multidrug-resistant Staphylococcus aureus strain MRSA252 was used. The photodynamic therapy (PDT) group was treated with different concentrations of TBO (0.5, 0.75, 1.0 or 1.25 µM) and different doses of red light (635 ± 5 nm wavelength; 30 or 50 J/cm²). The biofilms viability after PDT were evaluated by crystal violet (CV) staining assay and {2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino)carbonyl]-2H-tetra-zolium hydroxide} (XTT) assay; meanwhile, the morphological changes were detected by confocal laser scanning microscopy (CLSM) and scanning electron microscopy (SEM), separately. Moreover, the biofilms virulence was evaluated by red blood cell (RBC) hemolysis assay and staphylococcal virulence factor enterotoxins A (SEA) detected by enzyme linked immunosorbent assay (ELISA). After PDT, the biofilm was re-cultured for extra 48 h. Its formation viability and virulence were detected again. All data were analyzed by ANOVAs followed by the Games Howell post hoc test (α = 0.05).ResultsThe biofilm was inactivated about 2.3 log10 at 1.25 µM with 30 J/cm² illumination, and 3.5 log10 with 50 J/cm² after PDT (P<0.05). XTT assays demonstrated the viability of mature MRSA biofilms was reduced after PACT. PDT group shows a distinct reduction in RBC hemolysis rate and the concentration of SEA compared to the control groups. The morphological features of the biofilms showed great changes, such as shrinkage, fissure, fragmentation, and rarefaction after being treated by TBO-PDT and observed by SEM. The recovery of the structure and virulence of biofilm were suppressed after PDT.ConclusionTBO-mediated PDT could destroy the biofilm structure, reduce its virulence and depress its self-recovery.     

Effect of methylene blue-induced photodynamic therapy on a Streptococcus mutans biofilm model

BackgroundSeveral studies have reported the use of antimicrobial photodynamic therapy (aPDT) to control biofilm but its efficacy depends on several factors, such as biofilm model used. This study aims to examine whether exposure to diode laser combined with methylene blue affects the bacterial viability and polysaccharide content in a Streptococcus mutans cariogenic biofilm model, which simulated ‘feast-famine’ episodes of exposure to sucrose that occur in the oral cavity.Materials and methodsS. mutans biofilms were formed on acrylic resin discs and exposed to a 10% sucrose solution for 1 min, eight times/day. After growing for 48 h, the biofilms were submitted to the following treatments, twice daily (n = 4): (i) 0.9% NaCl (NaCl) as the negative control; (ii) 0.12% chlorhexidine digluconate (CHX) as the positive antibacterial control; (iii) diode laser combined with methylene blue, using an energy density of 320 J/cm² (aPDT). After 120 h of growth, the biofilm formed on each disc was collected to determine the viable bacterial counts and concentration of insoluble exopolysaccharides (IEPS) and intracellular polysaccharides (IPS).ResultsBacterial counts in the biofilms formed differed among the treatments. Compared with NaCl, aPDT significantly destabilized biofilm (p < 0.0001). aPDT and CHX equally lowered the concentration of IEPS and IPS in biofilms.ConclusionUnder the experimental conditions assessed, our findings indicate that a twice-daily treatment with diode laser combined with methylene blue effectively decreased bacterial viability and the intra- and extracellular polysaccharide concentration in biofilms of S. mutans, a cariogenic bacterium.     

Antifungal effect of a new photosensitizer derived from BODIPY on Candida albicans biofilms

BackgroundPhotodynamic therapy (PDT) may be an alternative treatment of Candida albicans (C. albicans) infections. The aim of this study was to investigate the antifungal effect of PDT mediated by a new photosensitizer (PS) derived from BODIPY (BDP-4L) on C. albicans biofilms.MethodsC. albicans biofilms were incubated with BDP-4L of different concentrations and then irradiated at the light doses of 1.8, 3.6, 5.4, 7.2 and 9.0 J/cm². XTT reduction assay was conducted to determine the PS concentration and PDT parameters. Confocal light scanning microscopy (CLSM) and scanning electron microscope (SEM) were used to visualize and quantify the effect of BDP-4L on C. albicans biofilms after PDT.ResultsC. albicans biofilms were inactivated in light dose-dependent and PS concentration-dependent manners using BDP-4L as PS. Without irradiation, no inactivation effect was observed when PS concentrations varied from 5 μM to 80 μM. 40 μM PS with 3.6 J/cm² irradiation resulted in a significant reduction of 83.8% in biofilm metabolic activities. CLSM assay demonstrated that cell viability was obviously inhibited by 82.6%. SEM images revealed ruptured and rough cell surface, indicating increased cell membrane permeability after PDT.ConclusionsOur results suggested that BDP-4L mediated PDT exhibited a favorable antifungal effect on C. albicans biofilms.     

Novel cationic-chalcone phthalocyanines for photodynamic therapy eradication of S. aureus and E. coli bacterial biofilms and MCF-7 breast cancer

New tetrasubstituted zinc (II) and indium (III) phthalocyanines bearing dimethylamino chalcone group (complexes 3 and 4) as well as their quaternized analogs (3a and 4a) have been assessed for their photodynamic therapy (PDT) of cancer as well as photodynamic antimicrobial chemotherapy activities against biofilms and planktonic cultures of pathogenic bacteria of Staphylococcus aureus and Escherichia coli. Compared to the non-quaternized phthalocyanines 3 and 4, the cationic phthalocyanines 3a and 4a exhibit a higher photodynamic inactivation against the planktonic cells with log reduction values above 9 at a concentration of 1.25 µM. This was attributed to the positive charge which enhances cellular uptake. More interestingly, 3a and 4a show a higher photodynamic inactivation (less than 3% of S. aureus survived) on their biofilm counterparts thanks to their stronger affinity to these cells. 3a and 4a Pcs also exhibited interesting PDT activity against MCF-7 cancer cells giving IC₅₀ values of 17.9 and 7.4 μM, respectively following 15 min irradiation. The obtained results in this work show that the positively charged phthalocyanines 3a and 4a are potential antibacterial photosensitizers that show some selectivity toward the Gram-positive and Gram-negative bacteria as well as MCF-7 breasts cancer cells.     

Microfluidic system with light intensity filters facilitating the application of photodynamic therapy for high-throughput drug screening

Background: Photodynamic therapy utilizes light energy with a photosensitizer (a light-sensitive drug) to kill cancer cells through creation of singlet oxygen via light activation. When a photosensitizer is injected into the bloodstream and exposed to a specific wavelength of light, it generates oxygen to destroy or damage nearby cancer cells, while minimizing side effects on normal cells. Although photodynamic therapy is effective for treating cancer, various parameters, such as the optimum light intensity and photosensitizer dose, are currently poorly understood due to the complexity of conventional experimental schemes.Methods: To effectively perform a simultaneous single parallel test for several different light irradiation conditions on each cell, a microfluidic device was developed to generate eight different intensities from a single light-emitting diode source, through eight different color dye concentrations functioning as light intensity filters. To show that this novel high-throughput microfluidic system can analyze the effects of various light intensities during photodynamic therapy, the optimum light intensities and photosensitizer doses were determined for two different cancer cell lines.Results: Optimum light intensities and photosensitizer were determined for all cell lines. The photodynamic therapy effects in response to different irradiated light intensities were characterized by analyzing cell viability after photosensitizer treatmentConclusions: The developed platform is capable of being used as a photodynamic therapy screening tool. The proposed platform provides a simple and robust way to optimize the combined parameters of light intensity and dosage for diverse types of cancer cells.     

Antimicrobial photothermal therapy using diode laser with indocyanine green on Streptococcus gordonii biofilm attached to zirconia surface

PurposeThe purpose of this study was to evaluate the antimicrobial effects of photothermal therapy using indocyanine green (ICG) and an 810-nm infrared diode laser on Streptococcus gordonii biofilm attached to zirconia surfaces in vitro.MethodsA biofilm was formed using the static method on zirconia disks placed in a 24-well plate. The biofilms were subdivided into the following six treatment groups: control, commercial photodynamic therapy (PDT), chlorhexidine gluconate (CHX), laser only (L, 810-nm infrared diode), ICG, and laser with ICG (PTT). After treatment, each disk was agitated and the solution with detached bacteria was spread directly on a blood agar plate. Cells were cultured under anaerobic conditions and colony-forming units were counted. Confocal laser-scanning microscopy was used to assess the survival according to the height of the biofilm.ResultsThe PTT, PDT, and CHX groups showed a significant reduction in S. gordonii viability (p<0.05), while the L and ICG groups showed no significant difference compared to the control group (p = 0.32, p = 0.97; respectively). In confocal laser-scanning microscopy images, the PTT, PDT, and CHX groups presented most of the dead bacteria in both the upper and lower levels of biofilm.ConclusionWithin the limitations of this in vitro study, PTT with ICG was effective in significantly reducing the viability of S. gordonii bacteria on zirconia. Further studies are needed to establish a standardized PTT protocol to treat peri‑implant diseases.     

Photodynamic antimicrobial chemotherapy with asymmetrical cationic or neutral metallophthalocyanines conjugated to amino-functionalized zinc oxide nanoparticles (spherical or pyramidal) against planktonic and biofilm microbial cultures

The synthesis and characterization of neutral zinc and indium substituted mercaptobenzothiazole substituted phthalocyanines (Pcs) and their respective cationic derivatives are presented. The phthalocyanines were further covalently linked to two differently shaped amino-functionalized ZnO nanoparticles (ZnONPs): namely nanospheres (NH₂-ZnONSp), and nanopyramids (NH₂-ZnONPy), to form corresponding nanoconjugates. The photophysicochemical properties of each nanocomposite were determined, and the Pc-ZnONPs produced high singlet oxygen quantum yields. The photodynamic antimicrobial chemotherapy activity was determined using planktonic and biofilm cells of Staphylococcus aureus (S. aureus), Escherichia coli (E. coli), and Candida albicans (C. albicans). The conjugates of the cationic Pc derivatives with ZnONPy produced the highest log reduction values (∼ 8 and above) with the complete elimination of all planktonic cells at 0.45 kJ/cm² for S. aureus and at 0.9 kJ/cm² for E. coli, and C. albicans. For biofilms log reduction values >3 for both S. aureus and E. coli were obtained. The conjugates of the cationic Pc derivatives with NH₂-ZnONPy showed great potential in eradicating mixed microbial biofilms.     

Mechanisms in photodynamic therapy: part one—photosensitizers, photochemistry and cellular localization

The use of non-toxic dyes or photosensitizers (PS) in combination with harmless visible light that is known as photodynamic therapy (PDT) has been known for over a hundred years, but is only now becoming widely used. Originally developed as a tumor therapy, some of its most successful applications are for non-malignant disease. In a series of three reviews we will discuss the mechanisms that operate in the field of PDT. Part one discusses the recent explosion in discovery and chemical synthesis of new PS. Some guidelines on how to choose an ideal PS for a particular application are presented. The photochemistry and photophysics of PS and the two pathways known as Type I (radicals and reactive oxygen species) and Type II (singlet oxygen) photochemical processes are discussed. To carry out PDT effectively in vivo, it is necessary to ensure sufficient light reaches all the diseased tissue. This involves understanding how light travels within various tissues and the relative effects of absorption and scattering. The fact that most of the PS are also fluorescent allows various optical imaging and monitoring strategies to be combined with PDT. The most important factor governing the outcome of PDT is how the PS interacts with cells in the target tissue or tumor, and the key aspect of this interaction is the subcellular localization of the PS. Examples of PS that localize in mitochondria, lysosomes, endoplasmic reticulum, Golgi apparatus and plasma membranes are given. Finally the use of 5-aminolevulinic acid as a natural precursor of the heme biosynthetic pathway, stimulates accumulation of the PS protoporphyrin IX is described.     

Antimicrobial photodynamic effect of phenothiazinic photosensitizers in formulations with ethanol on Pseudomonas aeruginosa biofilms

Background dataMethylene blue (MB) and toluidine blue (TB) are recognized as safe photosensitizers (Ps) for use in humans. The clinical effectiveness of the antimicrobial photodynamic therapy with MB and TB needs to be optimized, and ethanol can increase their antimicrobial effect. Formulations of MB and TB containing ethanol were evaluated for their ability to produce singlet oxygen and their antibacterial effect on Pseudomonas aeruginosa biofilms.MethodsPhotoactivated formulations were prepared by diluting the Ps (250 μM) in buffered water (pH 5.6, sodium acetate/acetic acid), 10% ethanol (buffer: ethanol, 90:10), or 20% ethanol (buffer: ethanol, 80:20). Biofilms also were exposed to the buffer, 10% ethanol, or 20% ethanol without photoactivation. Untreated biofilm was considered the control group. The production of singlet oxygen in the formulations was measured based on the photo-oxidation of 1,3-diphenylisobenzofuran. The photo-oxidation and CFU (log₁₀) data were evaluated by two-way ANOVA and post-hoc Tukey’s tests.ResultsIn all the formulations, compared to TB, MB showed higher production of singlet oxygen. In the absence of photoactivation, neither the buffer nor the 10% ethanol solution showed any antimicrobial effect, while the 20% ethanol solution significantly reduced bacterial viability (P = 0.009). With photoactivation, only the formulations containing MB and both 10% and 20% ethanol solutions significantly reduced the viability of P. aeruginosa biofilms when compared with the control.ConclusionsMB formulations containing ethanol enhanced the antimicrobial effect of the photodynamic therapy against P. aeruginosa biofilms in vitro.     

Curcumin-loaded multifunctional chitosan gold nanoparticles: An enhanced PDT/PTT dual-modal phototherapeutic and pH-responsive antimicrobial agent

Overuse of antibiotics has led to the emergence of multidrug resistant (MDR) bacteria.. Photothermal (PTT) and photodynamic therapy (PDT) have may be effective alternatives for antibiotics in the treatment of bacterial infections. In this study, based on chitosan (CS)-coated gold nanoparticles, a pH stimulus-responsive drug delivery system was developed, which can anchor to the cell membrane for photodynamic therapy and photothermal therapy, and enhance the therapeutic potential of curcumin (Cur). Release experiments showed that AuNPs/CS-Cur nanocomposites released curcumin in a pH-dependent manner, which may facilitate the drug to be delivered to the acidic bacterial infection environment. CS as the outer layer covered on gold nanoparticles could improve the dispersibility of Cur in aqueous solution, gold nanoparticles prevent rapid photobleaching of curcumin, thus ensuring the yield of singlet oxygen under irradiation, and enhance the electrostatic binding with bacteria cell membrane. Under light conditions, AuNPs/CS-Cur can produce a large amount of reactive oxygen species and heat to kill S. aureus and E. coli. Compared with free Cur-mediated PDT, the complex significantly improved the synergistic PTT/PDT photoinactivation ability against S. aureus and E. coli. In addition, AuNPs/CS-Cur had good biocompatibility. Therefore, AuNPs/CS-Cur possessed the characteristics of electrostatic targeting, photodynamic and photothermal antibacterial therapy, which would become an efficient and safe antibacterial nano-platform and provide new ideas for the treatment of bacterial infection.     

光动力抗微生物化学疗法治疗体内感染的研究进展

由于世界范围内微生物的耐药性发展迅速,难治性的感染性疾病不断增多,目前迫切需要新的针对耐药微生物的治疗方法。光动力抗微生物化学疗法是基于光动力疗法的原理,通过光激活光敏剂以杀灭微生物的一种新的抗感染方式。这种治疗方式是一种很有发展前景的治疗难治性感染性疾病的新策略。本文为光动力抗微生物化学疗法对体内感染,尤其是难治性微生物感染研究的综述。