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.

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.

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.

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.

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.

万古霉素结合光热治疗协同抵抗金黄色葡萄球菌

目的 金黄色葡萄球菌感染对人体危害极大,而用抗生素治疗容易引起细菌耐药。因此,开发新型抗菌剂和抗菌模式迫在眉睫。方法 本文通过非键合功能化作用将万古霉素(Vancomycin,Van)结合在聚乙二醇功能化的氧化石墨烯(Graphene oxide,GO)表面,利用GO良好的光热转化性能,构建新型抗菌复合材料以对抗金黄色葡萄球菌感染,并通过紫外可见光谱、红外光谱及扫描电子显微镜等对其进行表征。结果 该抗菌复合材料不仅具有Van对金黄色葡萄球菌的抑制作用,同时在白光照射下还具有光热抗菌活性,这种光热-化学双重抗菌模式可有效抑制金黄色葡萄球菌的生长。该复合材料在光照下具有优异的光热转化活性,当其质量浓度≥4μg·mL^(-1)时,可有效抑制金光色葡萄球菌的生长,抑制质量浓度与不光照比较,降低了4倍。结论 该新型抗菌模式有望拓展Van等抗生素的应用。

Hepatocyte Growth Factor Is a Reliable Marker for Efficient Anti-Bacterial Therapy within the First Day of Treatment

Rapid diagnosis and choice of appropriate antibiotic treatment might be life-saving in serious infectious diseases. Still the available markers that can evaluate and monitor the diagnosis and treatment are few. Hepatocyte growth factor (HGF) has been studied as a potent regenerative factor produced and released during injuries such as infectious diseases. Monitoring of HGF levels might predict therapy results better than C-reactive protein (CRP) within the first day of treatment in pneumonia. For further investigation of previous observations we aimed to study HGF as a first-day marker in over-representing infectious diseases in comparison to procalcitonin (PCT), CRP and body temperature. Fifty-one patients with community acquired infectious diseases were included consequently at admittance and the serum samples were collected before and within 18 - 24 hours of treatment. HGF levels decreased significantly in case of efficient antibiotic therapy and HGF was shown to be better than PCT, CRP and body temperature to evaluate treatment. In patients with pneumonia, monitoring of HGF was most reasonable. HGF might be used as a therapeutic marker within the first day of empiric antibiotic treatment during infection.

抗菌光动力疗法辅助龈下刮治治疗慢性牙周炎临床效果观察

目的探讨抗菌光动力疗法(antibacterial photodynamic therapy,aPDT)辅助龈下刮治和根面平整(scaling and root planing,SRP)治疗慢性牙周炎的临床效果。方法本研究已通过单位伦理委员会审查通过,并获得患者知情同意。研究采用随机、对照分口设计,符合纳入标准的16例慢性牙周炎患者随机分为试验侧与对照侧。对照侧接受常规SRP,试验侧SRP基础上联合aPDT治疗(SRP+aPDT)。记录治疗前(基线)、治疗后1个月、3个月和6个月时牙周探诊深度(probing depth,PD)、菌斑指数(plaque index,PLI)、出血指数(bleed⁃ing index,BI)和探诊出血(bleeding on probing,BOP)阳性位点占比(BOP%)。结果13例患者完成了全部随访。对照侧356颗受试牙,2136个位点;试验侧360颗受试牙,2160个位点。治疗前,两侧基线水平各指标差异无统计学意义。在治疗后1个月、3个月和6个月时,试验侧和对照侧的牙周临床指标PD、PLI、BI、BOP%相较于治疗前均有明显改善(P<0.05)。在各时间点,与常规SRP相比,SRP+aPDT联合治疗侧PD、PLI和BI均有改善。SRP+aPDT联合治疗侧在治疗后3个月时BOP%和PLI的改善明显优于常规SRP侧(P<0.05)。结论aPDT辅助治疗慢性牙周炎可以在早期更好地改善牙龈出血,控制牙周炎症。

Photodynamic and photothermal therapies for bacterial infection treatment

Bacteria can cause numerous infectious diseases and has been a major threat to human humans.Although antibiotics have partially succeeded in treating bacteria,owing to antibiotic abuse,the emergence of multidrug-resistant(MDR)bacteria has drastically diminished their potency.Since the invention of laser,the combination of light and photosensitizers,photodynamic therapy(PDT),has become an effective noninvasive treatment along with photothermal therapy(PTT),in which heat is generated by nonradiative relaxation.Antimicrobial PDT and PTT are emerging as effective treatments for bacterial infection,particularly against MDR bacteria.This mini review covers the recent progresses in PDT and PTT for bacterial treatment.

二硫化钼在光动力疗法和光热疗法中的应用

综述了MoS_(2)在光动力疗法(PDT)和光热疗法(PTT)中的抗菌应用进展。MoS_(2)凭借其独特的层状结构和高活性位点,成为光驱动抗菌领域的高潜力材料。讨论了PDT与PTT的基本原理及其协同抗菌机制,分析了MoS_(2)的结构特性,展示了MoS_(2)在增强抗菌效果上的优势,并详细阐述了其在PDT、PTT及协同抗菌中的具体应用。然而,当前应用仍面临氧化降解、易聚集、靶向效率低及生物安全性等挑战。未来,需进一步优化MoS_(2)性能,加强安全性评估,以推动其在光驱动抗菌领域的广泛应用。

水凝胶中的抗菌技术

细菌感染及其耐药性是当今世界面临的巨大健康难题之一,每年给全世界造成了巨大的人员伤亡和经济损失。水凝胶是一种三维聚合物网络结构胶体,其亲水性好,具备独特的三维网络、良好的生物相容和细胞粘附性,因而水凝胶是一种适用于抗菌领域的新型生物材料,也有望于成为解决抗生素耐药性的潜力抗菌材料。根据相应的抗菌方式,水凝胶中的抗菌技术可以大致归纳为以下几类:(i)负载抗菌物质水凝胶;(ii)具有固有抗菌活性水凝胶;(iii)利用光响应疗法的抗菌水凝胶。文章简略介绍各种水凝胶抗菌技术的基本原理,方法和应用,并对未来存在的困难和挑战进行初步探讨。

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.

基于声动力和类酶活性的铌基涂层:抗菌及促进细胞增殖与分化

目前感染性骨缺损修复仍然是临床难题。本研究采用微弧氧化结合水热合成方法在纯铌表面原位构建氧化铌/硫化铁异质结涂层MN@FS。结果表明,该异质结不仅具有类酶活性,而且在超声作用下具有声动力性能。在模拟细菌感染的酸性条件下,超声可触发异质结声动力,并增强类氧化酶活性,产生多种活性氧以协同抗菌/清除细菌生物膜,其抑菌率和清除率分别为98.57%和91.43%。在模拟生理条件下,超声可触发异质结,增强其类抗氧化酶活性,清除活性氧,缓解氧化应激,促进骨髓间充质干细胞(rBMSCs)的增殖与成骨分化。综上,该涂层材料在感染性骨修复方面具有广阔的应用前景。

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.

基于迭代进化的肠出血性大肠杆菌噬菌体鸡尾酒的抗菌效果评价

分离到一株抗菌能力较差的新型噬菌体vB_EcoM_CRP22,通过模拟噬菌体与细菌在自然环境中的相互作用,开发了迭代适应性进化的方法使噬菌体感染噬菌体抗性突变菌株,显著提高了噬菌体对肠出血性大肠杆菌(EHEC)的抗菌效果,由噬菌体进化株组合成的鸡尾酒制剂感染细菌后36 h内能有效控制OD_(600)低于0.4。该实验为噬菌体疗法的发展提供了新思路。

光热疗法在种植体周疾病治疗中的应用策略

光热疗法(photothermal therapy,PTT)作为一种新兴的治疗技术,具有临床操作便捷、可控性良好和无创性、易被患者接受等特点,逐渐在口腔种植体周疾病的治疗中得到了关注。其中,近红外光响应的PTT良好地弥补了传统治疗方式中存在的强度、深度不足的问题。同时还具有减轻周围组织损伤、促进愈合等特点。本文对光热疗法在种植体周疾病中的应用策略进行综述,为其在口腔抗菌治疗领域的临床应用和发展提供参考。

还原型多金属氧酸盐协同光热治疗铁死亡抗菌机制的研究

由于细菌感染严重威胁着公众健康,且抗生素的滥用诱导细菌产生一定的耐药性,因此有效的抑制细菌已成为当前迫切需要解决的问题.通过简单的一锅法合成了还原型多金属氧酸盐(Fe⁃POM),因其在近红外光区吸收强烈,具有极佳的光热转化效率和良好的光热稳定性,可作为光热剂用于光热抗菌治疗.此外,由于还原型Fe⁃POM具有混合价态的Fe^(2+)/Fe^(3+),不仅能够催化活性氧(ROS)的产生,促使细菌脂质过氧化(LPO)增强,而且还会消耗谷胱甘肽(GSH),进而诱发细菌铁死亡.在细菌实验中,将Fe⁃POM(50μg/mL)与NIR⁃II光热结合协同处理细菌后,细菌的活力下降超过95%.因此,Fe⁃POM不仅能促进细菌诱发铁死亡机制,而且还可以作为一种光热试剂用于抗菌治疗,通过结合纳米材料和光热治疗的双重抗菌作用能够显著提高抗菌效果.

羟基咔咯及其金属配合物的合成与抗菌性能研究

为了寻找结构新颖、杀菌活性更好的光敏剂,以10-(4-羟基苯基)-5,15-二(五氟苯基)咔咯(P-OH)为先导化合物,进而合成了四种金属配合物10-(4-羟基苯基)-5,15-二(五氟苯基)咔咯镓(P-OH-Ga)、10-(4-羟基苯基)-5,15-二(五氟苯基)咔咯铜(P-OH-Cu)、10-(4-羟基苯基)-5,15-二(五氟苯基)咔咯铁(P-OH-Fe)和10-(4-羟基苯基)-5,15-二(五氟苯基)咔咯钴(P-OH-Co)。通过紫外-可见吸收光谱、荧光光谱等表征了P-OH、POH-Ga、P-OH-Cu、P-OH-Fe和P-OH-Co五种化合物的结构,并进一步研究其光动力抗菌性能。结果表明:在光照条件下,P-OH与P-OH-Ga在有光照射下的抗菌活性最强,咔咯中心引入镓离子能够增强其荧光发射强度及在可见光区的吸收;而引入铜、铁、钴离子后发生荧光淬灭,并且光动力抗菌活性有所减弱。对比之下,发现P-OH-Ga是一种更为优良的光动力抗菌试剂。

纳米光热材料在抗菌领域的研究进展

耐药菌的出现极大地提高了临床发病率及死亡率,并对人们的生活及医疗系统造成了很大的冲击。耐药菌的快速变异和新抗菌药研发的滞后,迫切需要新的抗菌手段以应对上述问题。光热疗法(PTT)是一种将太阳能转换成热能(光热转换),提高局部温度,进而杀死细菌的新型抗菌技术。PTT具有独特的抗菌机制,产生耐药菌的可能性较低,在抗菌领域具有独特的优势。各种具有光热转换效果的纳米粒子以及基于此设计的纳米复合材料是PTT的关键。该文综述了近年来光热剂(PTAs)在抗菌领域的研究进展,总结了PTAs的种类及应用领域,对PTT抗菌发展存在的问题进行了分析,对未来研究的重点和方向进行了展望,以期对PTAs抗菌材料的研究提供新的思路。

艾灸与还原氧化石墨烯/二氧化铈纳米复合材料修复感染性创面

背景:皮肤创伤修复过程复杂且易受感染,易导致预后不良,是目前创面修复研究的难点与热点,并受到中医药及组织工程研究领域的广泛关注。目的:观察艾灸和还原氧化石墨烯/二氧化铈纳米复合材料修复感染性创面的效果。方法:①采用水热法合成质量比分别为2∶1、1∶1和1∶2的还原氧化石墨烯/二氧化铈纳米复合材料,所得复合材料分别记为G2C1、G1C1和G1C2,检测3种材料的光热性能、细胞毒性及抗菌性能。取艾条,设置3种施灸距离(3.0-3.5 cm,记为灸1;2.5-3.0 cm,记为灸2;2.0-2.5 cm,记为灸3)对人体皮肤表面施灸10 min,检测光热性能;检测3种距离区间下实施艾灸的抗菌性能。同时,检测不同质量浓度G1C1材料、艾灸(3种施灸距离)及灸2+G1C1材料的大鼠背部体表红外热成像。②取60只成年SD大鼠,建立金黄色葡萄球菌感染创面模型,48 h后随机分10组干预,每组6只:对照组(不进行任何处理)、莫匹罗星组、灸2+G1C1组、灸1组、灸2组、灸3组及60,80,100,120μg/mL G1C1组(G1C1组给予808 nm近红外激光照射,10 min/次,每次治疗前在创面负载G1C1悬浮液;艾灸各组行原位悬起灸,干预时间10 min/次;灸2+G1C1组每次治疗前在在创面负载80μg/mL G1C1悬浮液,并用艾条行原位悬起灸,干预时间10 min/次),治疗频率2 d一次。干预7 d后,检测创面愈合情况、创面菌落计数及修复情况。结果与结论:①3种还原氧化石墨烯/二氧化铈纳米复合材料均具有良好的光热性能,复合材料质量浓度越高光热性能越好。灸2组施灸10 min温度能达到47.6℃,且不造成热损伤,更适合于动物实验。与NIH-3T3细胞共培养实验结果显示,60,80,100μg/mL G1C1具有良好的生物相容性。与金黄色葡萄球菌悬浮液共培养实验结果显示,G2C1、G1C1和G1C2均具有良好的抗菌作用,其中G1C1组表现出优异的抗菌性能,当其质量浓度为80μg/mL时抑菌率已达到100%。60-120μg/mL G1C1可有效清除金黄色葡萄球菌生物膜,材料质量浓度越高清除效果越好;艾灸也可有效清除金黄色葡萄球菌生物膜,且施灸距离越近清除效果越好。②莫匹罗星组、灸2组、灸2+G1C1组及80,100μg/mL G1C1组大鼠治疗第7天的创面面积相较于对照组明显减小,创面修复质量较好。莫匹罗星、G1C1、艾灸和灸2+G1C1均能有效清除创面细菌残留,且G1C1质量浓度越高细菌残留量越少,艾灸组施灸距离越近细菌残留量越少。其中80μg/mL G1C1组和灸2组的创面修复效率以及细菌残留量非常接近,且二者创面修复效率均优于莫匹罗星组。除此之外还观察到材料与艾灸联合后对创面细菌的清除能力要优于单独使用。③结果显示,艾灸、还原氧化石墨烯/二氧化铈纳米复合材料及其结合具有良好的抗感染和促创面愈合效果。