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Antibacterial wound dressings are confronted with the challenges in real-time imaging of infected wounds and effective removal of bacterial debris after sterilization to promote the healing process. Herein, injectable theranostic hydrogels were constructed from antimicrobial peptide ε-polylysine (ePL) and polydopamine (PDA) nanoparticles for real-time diagnosis of infected wounds, imaging-guided antibacterial photodynamic therapy (PDT), and on-demand removal of bacterial debris. Ureido-pyrimidinone was conjugated on ePL to produce PLU hydrogels through quadruple hydrogen bonding, and the inoculation of tetrakis(4-carboxyphenyl)porphyrin (TCPP)-loaded PDA (PTc) nanoparticles introduced Schiff base linkages in PLU@PTc hydrogels. The double-cross-linked networks enhance mechanical performance, adhesion strength, and self-healing properties of hydrogels, and the dynamic cross-linking enables their photothermal removal. The injection of PLU precursors and PTc NPs generates in situ sol-gel transformation, and the acid-triggered release of TCPP restores fluorescence emissions for real-time imaging of infected wounds under 410 nm illumination. Then, the released TCPP in the infected wounds is illuminated at 660 nm to launch a precise antibacterial PDT, which is strengthened by the bacterial capture on hydrogels. Hydrogels with wrapped bacterial debris are removed under illumination at 808 nm, and the hydrogel dressing change accelerates healing of infected wounds through simultaneous relief of oxidative stress, regulation of inflammatory factors, acceleration of collagen deposition, and promotion of angiogenesis. Thus, this study demonstrates a feasible strategy for wound infection theranostics through bacterial infection-triggered visual imaging, efficient nonantibiotic sterilization, and on-demand dressing change and bacterial debris removal.

The skin microbiota is an inseparable component of the skin barrier structure, which participates in the stabilization or impairment of the barrier function as well as the development of many skin diseases. In order to maintain the stability of skin bacteria community structure, people pay more and more attention to protecting probiotics, such as bacilli, and killing pathogens, such as Gram-positive cocci. We herein report a negatively charged photosensitizer TPA-3NBA with aggregation-induced emission (AIE) characteristics, which was synthesized by one-step reaction, can selectively and rapidly stain (within 0.5 min) and effectively kill Gram-positive cocci (killing 6.0 log 10 of Staphylococcus aureus at a concentration of 1 μM) without affecting bacilli under white light irradiation. This selective bacterial imaging makes it possible to quickly identify locally bacterial infection. Furthermore, the normal concentration of divalent ion (Ca2+) in human body can significantly promote the absorption of TPA-3NBA by Gram-positive cocci, thus improving its antibacterial activity. To the best of our knowledge, this is the first photosensitizer to be reported with good performance in selective bacterial imaging and removal of Gram-positive pathogenic cocci, indicating its potential application prospect in targeted antimicrobial therapy. [Display omitted] • TPA-3NBA with a negatively charged can rapidly and selectively stain and kill Gram-positive cocci. • The normal concentration of Ca2+ significantly promoted the absorption of TPA-3NBA by Gram-positive cocci. • Our negatively charged photosensitizers can be synthesized by one-step reaction. [ABSTRACT FROM AUTHOR]

• Novel nonperipheral 2-hydroxypyridine tetrasubstituted palladium(II) and nickel(II) phthalocyanines and their quarternized derivatives. • Photophysicochemical studies of the two new quarterner phthalocyanines. • Antibacterial efficiency of novel phthalocyanines against Gram (+) Methicillin-resistant Staphylococcus aureus (MRSA) and Gram (-) Aeromonas hydrophila through photodynamic therapy (PDT). Four novel tetra non-peripheral 2-hydroxypyridine substituted palladium (II) and nickel (II) phthalocyanines and their quaternized derivatives were synthesized. The phthalocyanines were fully characterized by different spectroscopic methods such as UV-Vis, FT-IR, 1H NMR and MALDI-TOF mass spectrometry. The quaternized phthalocyanines showed solubility in DMSO and water within a wide concentration range and with lack of aggregation behavior. The singlet oxygen generation properties were determined for quaternized phthalocyanine complexes in DMSO, water, and water + TritonX 100 solutions. The uptake capability and in vitro photodynamic activity studies performed on two pathogenic bacteria namely Gram (+) Methicillin-resistant Staphylococcus aureus (MRSA) and Gram (-) Aeromonas hydrophila suggested good potential of palladium (II) phthalocyanine complex (5) for the uptake and inactivation of planktonic cultured bacteria. Significant localization of water-soluble Pd(II) phthalocyanine complex was observed for MRSA biofilms. However, this resulted in low efficiency of pathogen inactivation. The newly synthesized nickel (II) phthalocyanine (6) showed lack of inactivation towards both bacterial strains under the applied mild treatment conditions. [ABSTRACT FROM AUTHOR]

Several photosensitizers have recently been proposed as novel approaches against β-lactamase-producing drug-resistant bacteria. However, these reported photosensitizers are rarely used for accurate recognition of drug-resistant bacteria. To tackle this challenge, the structurally modified photosensitizer CySG-2 based on a lipophilic cationic heptamethine indocyanine near-infrared (NIR) dye (IR-780) and an important synthesis intermediate of cephalosporin antibiotic (GCLE) not only achieved the accurate recognition of TEM-1 methicillin-resistant Staphylococcus aureus (MRSA) successfully but also achieved antimicrobial photodynamic therapy (aPDT) in animal models infected by drug-resistant bacteria. Accurate enzyme recognition and efficient photodynamic therapy capabilities allow CySG-2 to achieve one stone with two birds. In addition, CySG-2 could also promote the eradication of internalized MRSA by facilitating the autophagy process, which is synergistic with its capacity of inducing reactive oxygen species generation under NIR laser irradiation for aPDT. Collectively, it is an effective multifunctional photosensitizer with the potential ability to guide the optimal use of different antibiotics and apply them in clinical treatment.

[Display omitted] • Methylene blue and surfactin could form complex through electrostatic interaction. • Surfactin-methylene blue complex could accumulate efficiently into bacterial cells. • Surfactin-methylene blue complex showed the higher APDT efficiency. • Surfactin-methylene blue complex could target intracellular proteins. Recently, increased attention has been focused on antibacterial photodynamic therapy (APDT) to treat multidrug-resistant bacterial infection due to the antibiotic abuse. Methylene blue has been used as a kind of efficient and cheap commercial photosensitizer in APDT. However, due to high hydrophilicity, methylene blue is not able to be transcellular intaken and accumulated efficiently. To promote accumulation and APDT efficiency of methylene blue, lipopeptide surfactin-methylene blue complex has been prepared through electrostatic interaction. The complex under LED irradiation was found to effectively reduce 5.0 Log 10 CFU and 7.6 Log 10 CFU for P. aeruginosa and S. aureus , respectively. The bacterial reduction efficiency is slightly higher than free methylene blue. The photosensitizers accumulation and APDT targeting protein have been characterized by fluorescence spectroscopy, fluorescence microscopy and protein electrophoresis techniques. These results demonstrated that more surfactin-methylene blue complex could be accumulated more into the cell, and inactivate bacteria through destroying intracellular protein under LED illumination. In comparison, free methylene blue under light could inactivate bacteria through destroying membrane protein and lipid structures. These results would provide valuable insight for developing advanced clinical medicine and designing photo-drug for photodynamic therapy. [ABSTRACT FROM AUTHOR]

Antibacterial photodynamic therapy (aPDT) has emerged as an attractive treatment option for efficient removal of pathogenic bacteria. However, aPDT in deep tissue will encounter difficulties such as limited light penetration depth, insufficient oxygen (O 2 ) supply and inability to eliminate inflammation introduced by bacteria, which hinders its clinical application. Herein, the near infrared (NIR) strategy of simultaneously generating O 2 and CO was developed for aPDT based antibacterial therapy and mitigation of deep infection inflammation. Methods: We prepared NIR-mediated multifunctional aPDT nanoplatform (POS-UCNPs/ICG) producing therapeutic gas of O 2 and CO. The CO, O 2 and ROS generation of the nanoplatform were characterized by dye probes, respectively. The antibacterial activity and anti-inflammation of POS-UCNPs/ICG were demonstrated in vitro and in vivo . In addition, the therapeutic effects in vivo were serially analyzed by immunofluorescence staining, Masson's staining, hematoxylin and eosin staining, colony formation units (CFU) and so on. Results: NIR-mediated multifunctional aPDT nanoplatform was realized by combining the up-conversion nanoparticles (UCNPs) and partially oxidized SnS 2 (POS) nanosheets (NSs) as well as indocyanine green (ICG). Using a single 808 nm light, aPDT can be achieved via ICG molecules, meanwhile, O 2 /CO can be generated by POS NSs through upconversion light excitation. During the aPDT process, O 2 can enhance aPDT, while CO can regulate inflammation through the PI3K/NF-κB pathway. Therefore, POS-UCNPs/ICG groups had a highest percentage of healing area up to 91.55±1.26% in mouse abscess model. Conclusion: Due to enhanced aPDT and anti-inflammatory collaborative therapy, the POS-UCNPs/ICG composites showed remarkably accelerated recovery in animal abscess models. Such NIR light responsive nanoplatform with optimized antibacterial capacity and immunomodulatory functions is promising for clinical therapeutics of bacteria-induced infections., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

• Commercially available powdered Curcuma and Chlorella extracts could act as photosensitizers in aPDT. • aPDT with a 405 nm light source and Curcuma and Chlorella as photosensitizers exhibits significant antibacterial effects against S. mutans biofilm. • aPDT employing natural plant extracts as photosensitizers can be used as a strategy for preventing dental caries. Antimicrobial photodynamic therapy (aPDT) using natural photosensitive agents is an effective method for preventing oral diseases of bacterial origin. The purpose of this study was to evaluate the antimicrobial effect of aPDT, using powdered extracts of Chlorella and Curcuma, on the biofilms of Streptococcus mutans (S. mutans), a bacterium that is known to cause dental caries. Commercially available powdered Chlorella and Curcuma extracts were used as photosensitizers. S. mutans , cultured for 2 days, was inoculated (0.1 ml; 1 × 109 CFU/ml) on the surface of a hydroxyapatite (HA) disc and incubated for 24 h to allow the formation of a biofilm. The HA disc with the S. mutans biofilm was immersed in either Curcuma extract (0.5 mg/ml), Chlorella extract, distilled water (negative control), or Listerine (positive control) for 1 min and then irradiated with an LED (Qraycam; wavelength, 405 nm; energy, 59 mW) for 5 min. The application of aPDT with Curcuma or Chlorella extract to S. mutans 24-hour biofilms significantly decreased the number of viable cells and the live/dead cell ratio when compared with those in the negative control (distilled water; p < 0.05). aPDT using 405 nm light and Chlorella or Curcuma as a photosensitizer has significant antimicrobial effects against S. mutans biofilms. Thus, employing aPDT with natural plant extracts as photosensitizers could be an effective strategy for preventing dental caries but needs to be evaluated in properly controlled clinical trials.. [ABSTRACT FROM AUTHOR]

Aim: This study aimed to determine the feasibility and first efficacy of indocyanine green (ICG)-assisted antimicrobial photodynamictherapy (aPDT) as activated using LED light to the dental plaque. Methods: Fifteen healthy adults were assigned to this four-day randomized study. After rinsing with ICG, 100 J/cm2 of 810 nm LED light was applied to the aPDT-treatment area. Plaque area and gingival crevicular fluid (GCF) matrix metalloproteinase-8 (MMP-8) were measured, and plaque bacteriomes before and after the study were analyzed using 16S rRNA sequencing. Results: aPDT administration was preformed successfully and plaque-specifically with the combination of ICG and the applicator. Total plaque area and endpoint MMP-8 levels were reduced on the aPDT-treatment side. aPDT reduced Streptococcus, Acinetobacteria, Capnocytophaga, and Rothia bacteria species in plaques. Conclusion: ICG-assisted aPDT reduces plaque forming bacteria and exerts anti-inflammatory and anti-proteolytic effects. [ABSTRACT FROM AUTHOR]

Helicobacter pylori (H. pylori) infection is closely associated with the development of gastric inflammatory diseases and cancer. However, the continued abuse and misuse of antibiotics has accelerated the spread of antibiotic-resistant strains, which poses a tremendous challenge for antibiotic-based H. pylori treatment. In this study, a H. pylori -targeting photodynamic therapy (PDT) system is proposed that multiple 3′-sialyllactose (3SL)-conjugated, poly- l -lysine-based photosensitizer (p3SLP). p3SLP facilitates H. pylori -targeting PDT via the specific interaction between 3SL and sialic acid-binding adhesin (SabA) in the H. pylori membrane. p3SLP can be orally administered to H. pylori infected mice and irradiated using an endoscopic laser system. The gastrointestinal pathological analysis of the H. pylori -infected mice demonstrated significant H. pylori specific antibacterial effects of PDT without side effects to normal tissue. In addition, an anti-inflammatory response was observed at the site of infection after p3SLP treatment. Consequently, this study demonstrates the superior efficacy of anti- H. pylori PDT with p3SLP in H. pylori -infected mice, and this approach shows great potential for replacing antibiotic-based therapy. [ABSTRACT FROM AUTHOR]

Antibacterial photodynamic therapy (aPDT) is of vital importance for the treatment of periodontal diseases due to its great potential on effective elimination of pathogenic bacteria via overwhelming reactive oxygen species (ROS) generation. However, the excessive ROS after the therapeutic process may impose an oxidative stress within periodontal pockets, consequently leading to an irreversible destroy in surrounding tissue and severely limit its biomedical applications. In this study, considering the contradiction between ROS in bacteriostasis and inflammation, the role of ROS in different temporal and spatial states has been fully studied. Accordingly, we have designed composite nanomaterials that can play ROS based aPDT and anti-inflammatory effect by eliminating ROS, taking account of different ratio of photosensitizer/ROS scavenger to realize a time-sequential manner. Herein, a simple multifunctional nanocomposite was fabricated by coating red light-excited photosensitizer chlorin e6 (Ce6) onto nanoceria, achieving simultaneous sterilization and inflammation elimination via a dual directional regulation effect. This nano-based platform could utilize the aPDT for antibacterial purpose in the first stage with red-light irradiation, and subsequently scavenge the residual ROS via nanoceria to modulate host immunity by down-regulating the M1 polarization (pro-inflammatory) of macrophages and up-regulating the M2 polarization (anti-inflammatory and regenerative) of macrophages. Moreover, the local ROS level induced by activated inflammation pathway can be adjusted in a very long time because of the charge conversion effect of CeO 2. The regenerative potential of inflammatory surrounding tissues was improved in the animal model. Our strategy will open a new inspiration to fight against the defects of aPDT in the treatment of periodontal disease, even in the anti-infection therapy for the future clinical application. Image 1 • A ceria@Ce6 multifunctional nanocomposite exerts synergistic antibacterial efficacy against periodontal pathogens at first stage. • This nano-based platform could subsequently scavenge the residual ROS via nanoceria for anti-inflammation. • The nanocomposite could modulate polarization of macrophages, thus alleviating inflammation and improving regeneration. • This strategy could fight against the defects of aPDT in treating infections particularly in periodontal diseases. • Abstract. [ABSTRACT FROM AUTHOR]

• New photoactive dendrimers PPI modified with 1,8-naphthalimides have been synthesised. • Antimicrobial and antiviral activity of dendrimers have been investigated. • 1,8-naphthalimide derivatives have been tested as active components in antibacterial photodynamic therapy. Through the peripheral modification of a first-generation polypropylene amine dendrimer two new photoactive dendrimers containing 4-dimethylamino-1,8-naphthalimide (3) and 3-bromo-4-dimethylamino-1,8-naphthalimide (4), have been obtained. Photophysical and spectral characteristics of these dendrimers were investigated in two organic solvents. We found that they absorb light in the visible spectral region and emit yellow-green fluorescence. Antimicrobial activity of dendrimers against pathogenic microorganisms has been investigated in solution and after deposition on a cotton fabric. For the first time, 1,8-naphthalimide derivatives have been tested as active components in antibacterial photodynamic therapy. To clarify the dendrimer effect, the results obtained were compared with those from two monomeric 1,8-naphthalimides (1 and 2) containing the same substitutes in the chromophore system. Cytotoxicity and antiviral activity of the dendrimers were also assessed. [ABSTRACT FROM AUTHOR]

Visible-light irradiation of porphyrin and metalloporphyrin dyes in the presence of molecular oxygen can result in the photocatalytic generation of singlet oxygen ( 1 O 2 ). This type II reactive oxygen species (ROS) finds many applications where the dye, also called the photosensitizer, is dissolved (i.e., homogeneous phase) along with the substrate to be oxidized. In contrast, metal-organic frameworks (MOFs) are insoluble (or will disassemble) when placed in a solvent. When stable as a suspension, MOFs adsorb a large amount of O 2 and photocatalytically generate 1 O 2 in a heterogeneous process efficiently. Considering the immense surface area and great capacity for gas adsorption of MOFs, they seem ideal candidates for this application. Very recently, covalent-organic frameworks (COFs), variants where reticulation relies on covalent rather than coordination bonds, have emerged as efficient photosensitizers. This comprehensive mini review describes recent developments in the use of porphyrin-based or porphyrin-containing MOFs and COFs, including nanosized versions, as heterogeneous photosensitizers of singlet oxygen toward antimicrobial applications.

Damage or injury to the skin creates wounds that are vulnerable to bacterial infection, which in turn retards the process of skin regeneration and wound healing. In patients with severe burns and those with chronic diseases, such as diabetes, skin infection by multidrug-resistant bacteria can be lethal. Therefore, a broad-spectrum therapy to effectively eradicate bacterial infection through a mechanism different from that of antibiotics is much sought after. We successfully synthesized antibacterial photodynamic gold nanoparticles (AP-AuNPs), which are self-assembled nanocomposites of an antibacterial photodynamic peptide and poly(ethylene glycol) (PEG)-stabilized AuNPs. The AP-AuNPs exhibited aqueous and light stability, a satisfactory generation of reactive oxygen species (ROS), and a remarkable antibacterial effect toward both Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli upon light irradiation. Moreover, the synthesized nanocomposites significantly inhibited bacterial growth and biofilm formation in vitro . Photodynamic antibacterial treatment accelerated the wound-healing rate in S. aureus infections, mimicking staphylococcal skin infections. Using a combination of the bactericidal effect of a peptide, the photodynamic effect of a photosensitizer, and the multivalency clustering on AuNPs for maximal antibacterial effect under light irradiation, we synthesized AP-AuNPs as a wound-dressing nanomaterial in skin infections to promote wound healing. Our findings indicate a promising strategy in the management of bacterial infections resulting from damaged skin tissue, an aspect that has not been fully explored by our peers.

Significant consumption of antibiotics has generated multidrug resistance in bacteria, which is a major menace to human beings. Antibacterial photodynamic therapy (aPDT) is a progressing technique for inhibition of bacterial infection with minimal side effects. Metals and delivering agents play a major role in aPDT efficiency. Herein, we report a formulation to enrich the antibacterial photodynamic therapy utilizing metallocatanionic vesicles (MCVs) against both Gram-positive and Gram-negative bacteria. These MCVs were synthesized by utilizing iron-based double-chain metallosurfactant [FeCPC(II)] as a cationic surfactant and AOT, a double-chain anionic surfactant. These synthesized MCV fractions were characterized by distinct techniques like DLS, zeta potential, FE-SEM, confocal microscopy, SAXS, and UV-Visible spectroscopy. Polyhedral-shaped MCVs with a size of 200 nm were formed, wherein the charge and size of the catanionic vesicle can be controlled by varying the mixing ratios. Both Gram-positive bacteria, i.e., methicillin-resistant Staphylococcus aureus (MRSA), and Gram-negative bacteria, i.e., Escherichia coli (E. coli) , were used for aPDT using Rose Bengal (RB) as a photosensitizer (PS) encapsulated in MCVs in the presence of a 532 nm wavelength laser. The aPDT against bacterial cells was evaluated for both dark and light toxicities. Pure MCVs also exhibited good antibacterial properties; however, much enhancement was observed in the presence of RB encapsulated in MCVs under light, where eradication of bacteria ( E. coli and MRSA) was achieved in 30 min. The observations demonstrated that it is the presence of metal that enhances the singlet oxygen quantum yield of RB and MCVs help in retarding self-quenching and enhanced solubilization of RB. The cationic surfactant-rich fraction shows strong adhesion toward bacteria via electrostatic interactions. The outcome of this research shows that these newly fabricated metal-based metallocatanionic vesicles were effective against both Gram-positive and Gram-negative bacteria using aPDT and must be exploited for clinical applications as well as an alternative for antibiotics in the future.

Photodynamic therapy (PDT) based periodontal disease treatment has received extensive attention. However, the deep tissue location of periodontal plaque makes the conventional PDT encounter a bottleneck. Herein, upconversion fluorescent nanomaterial with near-infrared light excitation was introduced into the treatment of periodontal disease, overcoming the limited tissue penetration depth of visible light in PDT. Photosensitizer Ce6 molecules were combined with upconversion nanoparticles (UCNPs) NaYF4:Yb,Er with a novel strategy. The hydrophobic UCNPs were modified with amphiphilic silane, utilizing the hydrophobic chain of the silane to bind to the hydrophobic groups of the UCNPs through a hydrophobic-hydrophobic interaction, and the Ce6 molecules were loaded in this hydrophobic layer. This achieves both the conversion of the hydrophobic to the hydrophilic surface and the loading of the oily photosensitizer molecules. Because the excitation position of the Ce6 molecule is in the red region, Mn ions were doped to enhance red light, and thus the improved PDT function. This Ce6 loaded UCNPs composites with efficient red upconversion luminescence show remarkable bacteriological therapeutic effect on Porphyromonas gingivalis, Prevotella intermedia and Fusobacterium nucleatum and the corresponding biofilms under 980 nm irradiation, indicating a high application prospect in the treatment of periodontal diseases. [ABSTRACT FROM AUTHOR]

Antibiotics are commonly used to control, treat, or prevent bacterial infections, however bacterial resistance to all known classes of traditional antibiotics has greatly increased in the past years especially in hospitals rendering certain therapies ineffective. To limit this emerging public health problem, there is a need to develop non-incursive, non-toxic, and new antimicrobial techniques that act more effectively and quicker than the current antibiotics. One of these effective techniques is antibacterial photodynamic therapy (aPDT). This review focuses on the application of porphyrins in the photo-inactivation of bacteria. Mechanisms of bacterial resistance and some of the current 'greener' methods of synthesis of meso-phenyl porphyrins are discussed. In addition, significance and limitations of aPDT are also discussed. Furthermore, we also elaborate on the current clinical applications and the future perspectives and directions of this non-antibiotic therapeutic strategy in combating infectious diseases. [ABSTRACT FROM AUTHOR]

Amplification of reactive oxygen species (ROS) generation through covalent conjugation of bovine serum albumin (BSA) with newly synthesized, ROS-producing carbon dots (CDs) upon visible light irradiation is reported for the first time. Derivatization of surface carboxyl functional groups of Anthrarufin-derived, green-emitting CD with the amine functionality of BSA ushers distinct changes in the photophysics of CD including an unprecedented ∼50 nm shift in its excitation maxima, decrease in fluorescence lifetime, and concomitant increase in ROS generation. Substantial conformational changes of BSA were witnessed upon conjugation with CD, rendering the BSA-CD conjugate resistant to pepsinolysis. A protease-proof nanoassembly was derived from the BSA-CD conjugate through desolvation that simultaneously hosts a prototype antibiotic and generates ROS with excellent efficiency, making it an attractive platform for antibacterial photodynamic therapy (A-PDT) applications. Systemic annihilation of both Gram-positive and -negative bacteria was achieved with the BSA-CD nanoassembly and envisioned as alternatives to traditional photosensitizers.

The fact that increasing antibiotic resistance of pathogenic bacteria and a lack of new potent broad-spectrum antibiotics call for the development of alternative approaches for treating infectious diseases. With the merits of great efficacy, safety, and facile implementation, antibacterial photodynamic therapy (APDT) represents an attractive modality for this purpose. Here, we report that the newly fabricated photodynamic chitosan nano-assembly, designated CS-Ce6, could synergistically kill antibiotic-resistant bacteria with superior potency to vancomycin. CS-Ce6 nano-assembly, obtained from covalent conjugate of chlorin e6 (Ce6) with chitosan, exhibited strong association with bacteria, thus altering their morphologies and mediating great delivery efficiency of Ce6. Upon light irradiation, localized generation of singlet oxygen by CS-Ce6 nano-assembly has a remarkable bactericidal effect toward both drug-resistance Gram-positive methicillin-resistant Staphylococcus aureus (MRSA) and Gram-negative Acinetobacter baumannii , which was greater than that the free Ce6 and antibiotics had. We also confirmed that APDT-treated MRSA neither developed resistance to APDT nor altered their resistance to methicillin. Our in vivo studies demonstrated that the CS-Ce6 nano-assembly had comparable therapeutic efficacy with vancomycin in MRSA-infected mice. These results suggest that APDT by photodynamic chitosan nano-assembly hold great potential in combating antibiotic-resistant bacteria and hopefully in reducing the need of antibiotics in the future.

The use of nanoparticles as a potential building block for photosensitizers has recently become a focus of interest in the field of photocatalysis and photodynamic therapy. Porphyrins and their derivatives are effective photosensitizers due to extended π-conjugated electronic structure, high molar absorption from visible to near-infrared spectrum, and high singlet oxygen quantum yields as well as chemical versatility. In this paper, we report a synthesis of self-assembled porphyrin nanoparticle photosensitizers using zinc meso-tetra(4-pyridyl)porphyrin (ZnTPyP) through a confined noncovalent self-assembly process. Scanning electron microscopy reveals formation of monodisperse cubic nanoparticles. UV-vis characterizations reveal that optical absorption of the nanoparticles exhibits a red shift due to noncovalent self-assembly of porphyrins, which not only effectively increase intensity of light absorption but also extend light absorption broadly covering visible light for enhanced photodynamic therapy. Electron spin-resonance spectroscopy (ESR) studies show the resultant porphyrin nanoparticles release a high yield of singlet oxygen. Nitric oxide (NO) coordinates to central metal Zn ions to form stabilized ZnTPyP@NO nanoparticles. We show that under light irradiation ZnTPyP@NO nanoparticles release highly reactive peroxynitrite molecules that exhibit enhanced antibacterial photodynamic therapy (APDT) activity. The ease of the synthesis of self-assembled porphyrin nanoparticles and light-triggered release of highly reactive moieties represent a completely different photosensitizer system for APDT application.

Antibacterial photodynamic therapy (APDT) has drawn increasing attention from the scientific society for its potential to effectively kill multidrug-resistant pathogenic bacteria and for its low tendency to induce drug resistance that bacteria can rapidly develop against traditional antibiotic therapy. The review summarizes the mechanism of action of APDT, the photosensitizers, the barriers to PS localization, the targets, the in vitro-, in vivo-, and clinical evidence, the current developments in terms of treating Gram-positive and Gram-negative bacteria, the limitations, as well as future perspectives. Relevance for patients: A structured overview of all important aspects of APDT is provided in the context of resistant bacterial species. The information presented is relevant and accessible for scientists as well as clinicians, whose joint effort is required to ensure that this technology benefits patients in the post-antibiotic era., Competing Interests: The authors declare that there are no conflicts of interest present.