Metallo-supramolecular nanofibers based on type-I photosensitizer for synergistic antibacterial therapy

Photodynamic therapy(PDT)has shown great merits in treating microbial in-fections due to its absence of bacterial resistance.However,the pronounced hypoxic microenvironment in the bacterial infections limits the therapeutic effi-ciency of traditional type-II PDT,which is highly dependent on oxygen.Here type-I photosensitizer BTZ_(n)-Py(n=8,20)coordinates with chemical antibacterial agent Agþto fabricate metallo-supramolecular nanofibers.Under light irradiation,the formed nanofibers could not only generate type-Ⅱ reactive oxygen species(ROS),1O2,but also produce type-I ROS O2^(•-)which addressed the hypoxic issues within infected tissues.Moreover,the acid-and photo-active Agþrelease from the nano-fibers endowed the metallo-supramolecular nanofibers with controlled release characteristic,which showed good biocompatibility to normal tissues.Owing to controlled Agþrelease and photoinduced type-I ROS,the in vitro and in vivo ex-periments confirmed the significantly synergistic antibacterial performance of the metallo-supramolecular fibers against both Gram-positive and Gram-negative bacteria.

Orthogonal Aza-BODIPY–BODIPY dyad as heavy-atom free photosensitizer for photo-initiated antibacterial therapy

Photodynamic antibacterial therapy shows great potential in bacterial infection and the reactive oxygen species(ROS)production of the photosensitizers is crucial for the therapeutic e®ect.Introducing heavy atoms is a common strategy to enhance photodynamic performance,while dark toxicity can be induced to impede further clinical application.Herein,a novel halogen-free photosensitizer Aza-BODIPY-BODIPY dyad NDB with an orthogonal molecular conguration was synthesized for photodynamic antibacterial therapy.The absorption and emission peaks of NDB photosensitizer in toluene were observed at 703 nm and 744 nm,respectively.The°uorescence(FL)lifetime was measured to be 2.8 ns in toluene.Under 730 nm laser illumination,the ROS generation capability of NDB was 3-fold higher than that of the commercial ICG.After nanoprecipitation,NDB NPs presented the advantages of high photothermal conversion e±ciency(39.1%),good photostability,and excellent biocompatibility.More importantly,in vitro antibacterial assay conrmed that the ROS and the heat generated by NDB NPs could extirpate methicillin-resistant S.aureus e®ectively upon exposure to 730 nm laser,suggesting the potential application of NDB NPs in photo-initiated antibacterial therapy.

Phthalocyanine self-assembled nanoparticles for type I photodynamic antibacterial therapy

Most photodynamic therapies(PDT)rely on reactive oxygen species(ROS)produced by type II mecha nisms.However,since the production of type I ROS is not limited by oxygen content,making it more favorable for antimicrobial phototherapy in complex microenvironments.Herein,we report a substituen cationization design strategy that not only improves the hydrophilicity of the prepared phthalocyanine molecule,but also promotes the electron transfer process in the photosensitizer,resulting in the strong type I photodynamic effect of the phthalocyanine self-assembled photosensitizer to efficiently generate O_(2)^(·-)under both normal and hypoxic conditions.This in combination with its excellent bacteria recogni tion capability derived from the cationic part on its surface and intrinsic photothermal therapy effect o the phthalocyanine macrocycle endows the phthalocyanine self-assembled photosensitizer with excellen phototherapeutic antimicrobial properties in preclinical models,effectively promoting the wound healing process.This work provides a promising strategy for designing efficient multi-mode photosensitizers.

Ultrasmall Fe-doped carbon dots nanozymes for photoenhanced antibacterial therapy and wound healing

Pathogenic bacteria pose a devastating threat to public health.However,because of the growing bacterial antibiotic resistance,there is an urgent need to develop alternative antibacterial strategies to the established antibiotics.Herein,iron-doped carbon dots(Fe-CDs,~3 nm)nanozymes with excellent photothermal conversion and photoenhanced enzyme-like properties are developed through a facile one-pot pyrolysis approach for synergistic efficient antibacterial therapy and wound healing.In particular,Fe doping endows CDs with photoenhanced peroxidase(POD)-like activity,which lead to the generation of heat and reactive oxygen species(ROS)for Gram-positive and Gram-negative bacteria killing.This study demonstrates Fe-CDs have significant wound healing efficiency of Fe-CDs by preventing infection,promoting fibroblast proliferation,angiogenesis,and collagen deposition.Furthermore,the ultrasmall size of Fe-CDs possesses good biocompatibility favoring clinical translation.We believe that the nanozyme-mediated therapeutic platform presented here is expected to show promising applications in antibacterial.

Photonic Crystal-Enhanced Photodynamic Antibacterial Therapy

Photodynamic antibacterial therapy(PDAT)is a kind of rejuvenating strategy that combats bacterial infection due to its admirable characteristics of noninvasiveness and broad-spectrum antibacterial capability.However,the efficiency of PDAT can be greatly hindered by limited light irradiation.Herein,we propose an enhanced PDAT by employing photonic composite films(PCFs)via slow photon and multiple scattering effects.The PCFs are obtained by UV light-initiated polymerization of poly(ethylene glycol)phenyl ether acrylate with a self-assembled SiO_(2)colloidal particle array,followed by the deposition of photosensitizers(PSs).The PCFs can prompt the PSs with matched absorption,which are deposited on their surface,to sufficiently utilize the incident light and generate more reactive oxygen species based on the slow photon phenomenon of photonic crystals and multiple scattering effects of the SiO_(2)colloidal particles.This finding demonstrates the great potential and significance of PCFs in the field of PDAT,which may reduce the requirements of excitation equipment and avoid damage to normal tissues from exposure to huge light energy.

A new class of nitrobenzoic acid-based AIE photosensitizers for highly efficient photodynamic antibacterial therapy

hotodynamic therapy(PDT)has been drawing more and more attention in the antibacterial field.Traditional photosensitizers(PSs)tend to aggregate in aqueous media,which reduces the generation of reactive oxygen species(ROS)and seriously affects the photodynamic efficacy.Many efforts have been made to prevent aggregation of traditional PSs.By contrast,aggregation-induced emission PSs(AIE-PSs)take advantage of aggregation to boost ROS generation and fluorescence intensity.However,the efficacies of the reported antibacterial AIE-PSs are poor.Herein,we report a new class of highly effective antibacterial AIE-PSs based on nitrobenzoic acid structure.TTVBA,a negatively charged AIE-PS,can not only selectively kill spherical bacteria(Staphylococcus aureus(S.aureus))rather than rod-shaped bacteria(Escherichia coli(E.coli)),but also be easily extended to several AIE-PSs(TTVBP1–3)with positive charges and broad-spectrum antibacterial activity.We demonstrate that TTVBP2 can kill3.0 log_(10)of S.aureus at very low concentration(125 nmol L^(-1)),TTVBP3 can kill 4.7 log_(10)of Staphylococcus epidermidis(S.epidermidis)at a concentration of 1μmol L^(-1)and 3.8 log_(10)of E.coli at 5μmol L^(-1),thus enabling them among the most effective antibacterial AIE-PSs reported so far.Meanwhile,these AIE-PSs exhibit excellent wash-free imaging ability for bacteria by simple mixing with bacteria.We thus envision that TTVBA,a nitrobenzoic acid-based extendable AIE-PS,provides a new route for the design of AIE-PSs in antibacterial treatment.

Near-infrared Aza-BODIPY Dyes Through Molecular Surgery for Enhanced Photothermal and Photodynamic Antibacterial Therapy

The widespread use of high-dose antibiotics will not only lead to the rapid acquisition of antibiotic resistance and increased incidence of drug-resistant bacterial infections, but also produce toxic side effects on normal tissues. Herein, two near-infrared dyes BDP-4PTZ and BDP-4DPA were synthesized, and the electron donors of diphenylamine and phenothiazine with the only difference of sulphur(S)-lock between the two phenyl rings were introduced onto the electron acceptor aza-dipyrromethene boron difluoride(aza-BODIPY) through molecular surgery. Through co-precipitation into nanoparticles(NPs), BDP-4PTZ NPs and BDP-4DPA NPs were fabricated with good biocompatibility. Upon 660 nm photoirradiation, BDP-4PTZ NPs and BDP-4DPA NPs showed excellent photothermal conversion efficiency(43% and 50%, respectively) and reactive oxygen species(ROS) production performance(ca. 3.6 and 6 times higher than that of indocyanine green, respectively). In vitro antibacterial experiments indicated that both NPs could effectively destroy the bacteria’s membrane to eradicate drug-resistant bacteria. Furthermore, the bacterial abscess was effectively eliminated after treatment with BDP-4DPA NPs under 660 nm photoirradiation without adverse effects. Thus, through molecular surgery, BDP-4DPA without the S-lock demonstrates synergistic photothermal and photodynamic antimicrobial activities, which is promising for further molecular design towards effective neo-antimicrobial phototherapy.

Meso-substituted cationic 3-and 4-N-Pyridylporphyrins and their Zn(II)derivatives for antibacterial photodynamic therapy

Photodynamic inactivation of microorganisms known as antibacterial photodynamic therapy(APDT)is one of the most promising and innovative approaches for the destruction of pathogenic microorganisms.Among the photosensitizers(PSs),compounds based on cationic porphyrins/metalloporphyrins are most successfully used to inactivate microorganisms.Series of meso-substituted cationic pyridylporphyrins and metalloporphyrins with various peripheral groups in the third and fourth positions of the pyrrole ring have been synthesized in Armenia.The aim of this work was to determine and test the most e®ective cationic porphyrins and metalloporphyrins with high photoactivity against Gram negative and Gram positive microorganisms.It was shown that the synthesized cationic pyridylporphyrins/metalloporphyrins exhibit a high degree of phototoxicity towards both types of bacteria,including the methicillinresistant S.aureus strain.Zinc complexes of porphyrins are more phototoxic than metal-free porphyrin analogs.The e®ectiveness of these Zn–metalloporphyrins on bacteria is consistent with the level of singlet oxygen generation.It was found that the high antibacterial activity of the studied cationic porphyrins/metalloporphyrins depends on four factors:the presence in the porphyrin macrocycle of a positive charge(+4),a central metal atom(Zn2þÞand hydrophobic peripheral functional groups as well as high values of quantum yields of singlet oxygen.The results indicate that meso-substituted cationic pyridylporphyrins/metalloporphyrins cannd wider application in photoinactivation of bacteria than anionic or neutral PSs usually used in APDT.

Recent progress on Sn_(3)O_(4)nanomaterials for photocatalytic applications

Tin(IV)oxide(Sn_(3)O_(4))is layered tin and exhibits mixed valence states.It has emerged as a highly promising visible-light pho-tocatalyst,attracting considerable attention.This comprehensive review is aimed at providing a detailed overview of the latest advance-ments in research,applications,advantages,and challenges associated with Sn_(3)O_(4)photocatalytic nanomaterials.The fundamental con-cepts and principles of Sn_(3)O_(4)are introduced.Sn_(3)O_(4)possesses a unique crystal structure and optoelectronic properties that allow it to ab-sorb visible light efficiently and generate photoexcited charge carriers that drive photocatalytic reactions.Subsequently,strategies for the control and improved performance of Sn_(3)O_(4)photocatalytic nanomaterials are discussed.Morphology control,ion doping,and hetero-structure construction are widely employed in the optimization of the photocatalytic performance of Sn_(3)O_(4)materials.The effective imple-mentation of these strategies improves the photocatalytic activity and stability of Sn_(3)O_(4)nanomaterials.Furthermore,the review explores the diverse applications of Sn_(3)O_(4)photocatalytic nanomaterials in various fields,such as photocatalytic degradation,photocatalytic hydro-gen production,photocatalytic reduction of carbon dioxide,solar cells,photocatalytic sterilization,and optoelectronic sensors.The discus-sion focuses on the potential of Sn_(3)O_(4)-based nanomaterials in these applications,highlighting their unique attributes and functionalities.Finally,the review provides an outlook on the future development directions in the field and offers guidance for the exploration and de-velopment of novel and efficient Sn_(3)O_(4)-based nanomaterials.Through the identification of emerging research areas and potential avenues for improvement,this review aims to stimulate further advancements in Sn_(3)O_(4)-based photocatalysis and facilitate the translation of this promising technology into practical applications.

The First Pilot Epigenetic Type Improvement of Neuropsychiatric Symptoms in a Polymorphic Dopamine D2 (-DRD2/ANKK (Taq1A)), OPRM1 (A/G), DRD3 (C/T), and MAOA (4R) Compromised Preadolescence Male with Putative PANDAS/CANS: Positive Clinical Outcome with Precision-Guided DNA Testing and Pro-Dopamine Regulation (KB220) and Antibacterial Therapies

Pediatric autoimmune neuropsychiatric disorders associated with or without streptococcal and other bacterial infections (PANDAS/CANS) are emerging as a featured pediatric disorder. Although there is some controversy regarding treatment approaches, especially related to the behavioral sequelae, we have hypothesized in other published work that it is characterized by the rapid onset of Reward Deficiency Syndrome (RDS) in children. We propose utilizing a multi-systems biological approach involving the coupling of genetic addiction risk testing and pro-dopamine regulation (KB220/POLYGEN®) to help induce “dopamine homeostasis” in patients with PANDAS, especially those with known DNA-induced hypodopaminergia. This case study examines a 12-year-old Caucasian male with no prior psychiatric issues who presented with a sudden onset of severe anxiety, depression, emotional liability, and suicidal ideation. The patient underwent genotyping and the genetic addiction risk score (GARS) testing, which revealed risk polymorphisms in the dopamine D2 (-DRD2/ANKK (Taq1A), OPRM1 (A/G), DRD3 (C/T), and MAOA (4R) genes. These polymorphisms have been linked to hypodopaminergia. The patient was subsequently placed on research ID-KB220ZPBMPOLY (POLYGEN®), and albeit the possibility of bias, based upon self and parental assessment, a marked rapid improvement in psychiatric symptoms was observed. In the second phase of treatment (102 days utilizing KB220), the patient received standard antibody testing, which was positive for Lyme. Antibacterial therapy started immediately, and KB220z was discontinued to provide a wash-out period. A monotonic trend analysis was performed on each outcome measure, and a consistently decreasing trend was observed utilizing antibacterial therapy. Our recommendation, albeit only one case, is to utilize and further research a combined therapeutic approach, involving precision-guided DNA testing and pro-dopamine regulation along with antibacterial therapy, as well as glutathione to address offensive enhanced cytokines, in patients with suspected PANDAS/CANS.

Cationic Conjugated Oligomers for Efficient and Rapid Antibacterial Photodynamic Therapy via Both Type Ⅰ and Type Ⅱ Pathways

Recently,photodynamic therapy(PDT)has attracted wide attention due to its less susceptibility to drug resistance,broad-spectrum biocidal activity and biosafety in normal tissues.However,the traditional photosensitizers(Ps)face the disadvantage of poor therapeutic efficacy due to the requirement of an aerobic environment to generate ^(1)O_(2) through Type Ⅱ pathway.Herein,we designed and synthesized a novel cationic conjugated oligomer oligo(phenylene vinylene)(OPV)and studied its antibacterial photodynamic activity against both Gram-negative Escherichia coli(E.coli)and Gram-positive bacteria methicillin-resistant Staphylococcus aureus(MRSA).Importantly,the OpV can rapidly produce reactive oxygen species(ROs)through double pathways,Type Ⅰ and Ⅱ mechanism under white light irradiation,and efficiently kill E.coli and MRSA at a nanomolar level.The dual type photosensitizing capability makes OPV promising for enhanced PDT to treat pathogens and tumors in complex environments.

PDA-BPs integrated mussel-inspired multifunctional hydrogel coating on PPENK implants for anti-tumor therapy,antibacterial infection and bone regeneration

Currently,many cancer patients with bone defects are still threatened by tumor recurrence,postoperative bacterial infection,and massive bone loss.Many methods have been studied to endow bone implants with biocompatibility,but it is difficult to find an implant material that can simultaneously solve the problems of anticancer,antibacterial and bone promotion.Here,a multifunctional gelatin methacrylate/dopamine methacrylate adhesive hydrogel coating containing 2D black phosphorus(BP)nanoparticle protected by polydopamine(pBP)is prepared by photocrosslinking to modify the surface of poly(aryl ether nitrile ketone)containing phthalazinone(PPENK)implant.The multifunctional hydrogel coating works in conjunction with pBP,which can deliver drug through photothermal mediation and kill bacteria through photodynamic therapy at the initial phase followed by promotion of osteointegration.In this design,photothermal effect of pBP control the release of doxorubicin hydrochloride loaded via electrostatic attraction.Meanwhile,pBP can generate reactive oxygen species(ROS)to eliminate bacterial infection under 808 nm laser.In the slow degradation process,pBP not only effectively consumes excess ROS and avoid apoptosis induced by ROS in normal cells,but also degrade into PO43to promote osteogenesis.In summary,nanocomposite hydrogel coatings provide a promising strategy for treatment of cancer patients with bone defects.

Translating bacteriophage-derived depolymerases into antibacterial therapeutics:Challenges and prospects

Predatory bacteriophages have evolved a vast array of depolymerases for bacteria capture and deprotection.These depolymerases are enzymes responsible for degrading diverse bacterial surface carbohydrates.They are exploited as antibiofilm agents and antimicrobial adjuvants while rarely inducing bacterial resistance,making them an invaluable asset in the era of antibiotic resistance.Numerous depolymerases have been investigated preclinically,with evidence indicating that depolymerases with appropriate dose regimens can safely and effectively combat different multidrug-resistant pathogens in animal infection models.Additionally,some formulation approaches have been developed for improved stability and activity of depolymerases.However,depolymerase formulation is limited to liquid dosage form and remains in its infancy,posing a significant hurdle to their clinical translation,compounded by challenges in their applicability and manufacturing.Future development must address these obstacles for clinical utility.Here,after unravelling the history,diversity,and therapeutic use of depolymerases,we summarized the preclinical efficacy and existing formulation findings of recombinant depolymerases.Finally,the challenges and perspectives of depolymerases as therapeutics for humans were assessed to provide insights for their further development.

Electron Reservoir MoO_(3-x)-Driven Cu^(+) Doped Nanozyme with Enhanced Antibacterial Activity via Disrupting Redox Homeostasis

Redox nanozymes offer an appealing reactive oxygen species(Ros)-based antibacterial strategy via disrupting intracellular homeostasis,however,they still face many obstacles such as low enzymic activity and irreversible loss of catalytic active center.Meanwhile,the antioxidant glutathione(GSH)overexpressed in infected sites would limit the therapy efficiency.Herein,we develop a multifunctional nanozyme based on copper(l)(Cut)ion doped MoO_(3-x)(Cut-MoO_(3-x))by a simple yet efficient oxygen vacancy-reduced strategy without any pretreatment or additional agents.The resultant Cu^(+)-MoO_(3-x) hybrid possesses enhanced peroxidase-like(POD-like)activity,rapid GSH-depleting function and biodegradable ability.It can achieve highly efficient elimination of Pseudomonas aeruginosa(P.aeruginosa)via disrupting cellular redox balance.

Ultrastable graphene isolated Au Ag nanoalloy for SERS biosensing and photothermal therapy of bacterial infection

Plasmonic metal nanomaterials with intrinsic surface–enhanced Raman scattering(SERS)and photothermal properties,especially AuAg nanoalloys with both the outstanding merits of Au and Ag nanocrystals,show huge application prospects in bacterial theranostics.However,the direct exposure of AuAg nanoalloys in external conditions probably cause undesirable reactions and poisonous metal ion leakage during SERS detection and photothermal antibacterial therapy process,which severely hinder bacterial theranostics applications.Herein,we report an ultrastable graphene–isolated AuAg nanoalloy(GAA)with AuAg core confined in few–layer graphitic shell as a versatile platform for bacterial detection and therapy.The encapsulation of graphene ensures the good stability of AuAg core,that its superior SERS and photothermal properties are therefore further guaranteed.GAA is used for SERS detection of two vital bacterial biomarkers(including corrosive cyanide and pyocyanin),exhibiting good SERS quantitative and multiplexing ability.GAA is further used for photothermal antibacterial therapy application,and ultrahigh antibacterial efficacies for both Gram–negative Escherichia coli and Gram–positive Staphylococcus aureus are achieved under 808 nm laser irradiation.This work proposes a valuable method to develop robust bacterial theranostic platform.

Rapid sterilisation and diabetic cutaneous regeneration using cascade bio-heterojunctions through glucose oxidase-primed therapy

The cutaneous wound in diabetic patients frequently encounters intractable pathogenic infections due to the hyperglycemia micromilieu which is conducive to bacterial growth and multiplication.Despite the extensive clinical use of antibiotics to treat bacterial infections,the emergence of drug-resistant and super pathogens as well as the potential side effects of antibiotics have elicited alarming challenges to public health.To address this daunting concern,we devise and develop a photo-activated cascade bio-heterojunctions(C-bio-HJs)for rapid sterilization and diabetic cutaneous regeneration.In the designed C-bio-HJs,photo-generated electron-hole pairs of graphite-phase carbon nitride(g-C_(3)N_(4))are effectively separated with the marriage of molybdenum disulfide(MoS_(2)),which achieves the augmented photodynamic antibacterial effect.Moreover,glucose oxidase(GOx)tethered on the bio-HJs catalyzes glucose into hydrogen peroxide(H_(2)O_(2))in diabetic wounds for starvation therapy.Furthermore,Mo4+enables the catalysis of H_(2)O_(2)into a highly effective hydroxyl radical(⋅OH)for chemodynamic-photothermal combined antibacterial therapy.Both in vitro and in vivo results authenticate the cascading antibacterial properties and skin regeneration-promoting effects of the C-bio-HJs,which provide a facile strategy to combat diabetic wound healing through the synergistic GOx-primed dynamic therapies.

Two-dimensional copper metal-organic frameworks as antibacterial agents for biofilm treatment

Metal-organic frameworks(MOFs)composed of functional metal ions/clusters and suitable bridging ligands are highly designable,which have shown excellent catalytic activity as nanozymes and are promising for antibacterial therapy.Herein,twodimensional(2D)copper MOF nanosheets(Cu-MOF NSs)as effective antibacterial agents were prepared through a simple onestep method.The 2D Cu-MOF NSs displayed a peroxidase-like activity toward H_(2)O_(2)decomposition into highly cytotoxic hydroxyl radicals(·OH).Notably,the 2D morphology of Cu-MOF NSs provides a high density of Cu^(2+)/Cu^(+)surface active sites,which could efficiently oxidize the proteins and lipids on the bacterial surface and induce the death of bacteria.It is found that the as-prepared 2D Cu-MOF NSs exhibited antibacterial properties against Staphylococcus aureus(S.aureus)and could efficiently eradicate the biofilm of S.aureus.Up to 99.9%bacteria were killed at a Cu-MOF concentration of 4μg/m L.This study opens a new avenue for the design of MOF-based antibacterial agents to combat pathogenic bacterial infections.

A new track for antibacterial treatment:Progress and challenges of using cytomembrane-based vesicles to combat bacteria

The emergence and re-emergence of antibiotic-resistant bacteria,especially superbugs,are leading to complicated infections that are increasingly difficult to treat.Therefore,novel alternative antimicrobial therapies are urgently needed to reduce the morbidity and mortality caused by antibiotic resistance.The development of biomimetic-based therapy is expected to provide innovative means for addressing this challenging task.As a kind of novel biomaterial,cytomembrane-based vesicles(MVs)continue to receive considerable attention in antimicrobial therapy owing to their inherent biocompatibility,design flexi-bility,and remarkable ability to interact with biological molecules or the surrounding environment.These remarkable cell-like properties and their inherent interaction with pathogens,toxins,and the immune system underlie MVs-based functional protein therapy and targeted delivery to develop advanced therapeutic strategies against bacterial infection.This review provides a fundamental under-standing of the characteristics and physiological functions of cytomembrane-based vesicles,focusing on their potential to combat bacterial infections,including detoxification,immune modulation,antibiotics delivery,and physical therapy.In addition,the future possibilities and remaining challenges for clinically implementing MVs in the field of antibacterial treatment are discussed.

Metal natural product complex Ru-procyanidins with quadruple enzymatic activity combat infections from drug-resistant bacteria

Bacterial infection hampers wound repair by impeding the healing process.Concurrently,inflammation at the wound site triggers the production of reactive oxygen species(ROS),causing oxidative stress and damage to proteins and cells.This can lead to chronic wounds,posing severe risks.Therefore,eliminating bacterial infection and reducing ROS levels are crucial for effective wound healing.Nanozymes,possessing enzyme-like catalytic activity,can convert endogenous substances into highly toxic substances,such as ROS,to combat bacteria and biofilms without inducing drug resistance.However,the current nanozyme model with single enzyme activity falls short of meeting the complex requirements of antimicrobial therapy.Thus,developing nanozymes with multiple enzymatic activities is essential.Herein,we engineered a novel metalloenzyme called Ru-procyanidin nanoparticles(Ru-PC NPs)with diverse enzymatic activities to aid wound healing and combat bacterial infections.Under acidic conditions,due to their glutathione(GSH)depletion and peroxidase(POD)-like activity,Ru-PC NPs combined with H2O2 exhibit excellent antibacterial effects.However,in a neutral environment,the Ru-PC NPs,with catalase(CAT)activity,decompose H2O2 to O2,alleviating hypoxia and ensuring a sufficient oxygen supply.Furthermore,Ru-PC NPs possess exceptional antioxidant capacity through their superior superoxide dismutase(SOD)enzyme activity,effectively scavenging excess ROS and reactive nitrogen species(RNS)in a neutral environment.This maintains the balance of the antioxidant system and prevents inflammation.Ru-PC NPs also promote the polarization of macrophages from M1 to M2,facilitating wound healing.More importantly,Ru-PC NPs show good biosafety with negligible toxicity.In vivo wound infection models have confirmed the efficacy of Ru-PC NPs in inhibiting bacterial infection and promoting wound healing.The focus of this work highlights the quadruple enzymatic activity of Ru-PC NPs and its potential to reduce inflammation and promote bacteria-infected wound healing.

Photodynamic eradication of intratumoral microbiota with bacteria-targeted micelles overcomes gemcitabine resistance of pancreatic cancer

Increasing evidence suggests that intratumoral microbiota plays a pivotal role in tumor progression,immunosurveillance,metastasis,and chemosensitivity.Particularly,in pancreatic ductal adenocarcinoma,tumor-resident Gammaproteobacteria could transform the chemotherapeutic drug gemcitabine(Gem)into its inactive form,thus rendering chemotherapy ineffective.Herein,a strategy for selectively eradicating intratumoral bacteria was described for overcoming Gem resistance in a pancreatic cancer animal model.An antimicrobial peptide was linked with photosensitizer through a poly(ethylene glycol)chain,which can self-assemble into micelles with a diameter of∼20 nm.The micelles could efficiently kill bacteria under light irradiation by inducing membrane depolarization,thereby inhibiting Gem metabolism.In a bacteria-resident pancreatic cancer animal model,the selective photodynamic eradication of intratumoral bacteria was demonstrated to efficiently reverse Gem resistance.This research highlights antibacterial photodynamic therapy as a promising adjuvant strategy for cancer therapy by modulating intratumoral microbiota.