具有ROS产生功能的生物材料在口腔感染性疾病中的应用

PAGEPAGE17具有ROS产生功能的生物材料在口腔感染性疾病中的应用[摘要]人类口腔是其固有微生物群与宿主之间微妙共生关系的家园，这种平衡很容易因局部或全身因素而被打破，导致一系列口腔疾病，如龋齿、牙周炎和牙髓感染等。活性氧（ROS）在宿主的先天免疫防御中发挥着关键作用。ROS引起脂质过氧化、损伤DNA和蛋白质等多种生物大分子，导致微生物的死亡和生物膜结构的破坏。因此，开发具有ROS产生功能的生物材料正成为治疗口腔感染的一种有前景的方法。本文根据ROS产生的不同原理，分类概述了ROS产生生物材料在口腔感染性疾病中的最新进展。[关键词]活性氧；口腔疾病；感染；生物材料ApplicationofBiomaterialswithROS-GeneratingFunctioninOralInfectiousDiseasescrelationshipbetweenitsindigenousmicrobiotaandthehost.Thisequilibriumcanbeeasilydisruptedbylocalorsystemicfactors,therebyprecipitatingaspectrumoforaldiseases,suchasdentalcaries,periodontitis,andpulpinfections.Reactiveoxygenspecies(ROS)playapivotalroleinthehost'sinnateimmunedefense.ROSinducelipidperoxidationanddamagevariousbiomacromolecules,includingDNAandproteins,leadingtomicrobialdeathanddisruptionofbiofilmstructures.Consequently,thedevelopmentofbiomaterialswithROS-generatingcapabilitiesisemergingasapromisingstrategyforthetreatmentoforalinfections.ThisarticleprovidesacategorizedoverviewofthelatestadvancementsinROS-generatingbiomaterialsfororalinfectiousdiseases,basedondifferentprinciplesofROSgeneration.[KeyWords]ROS;oraldiseases;infection;biomaterials

口腔感染性疾病是全球范围内广泛流行的健康问题，它们不仅损害了人们的口腔健康，还对全身健康和心理健康造成了深远的影响，并带来了沉重的经济负担ADDINEN.CITEADDINEN.CITE.DATA[1]。口腔感染的发病机制通常与致病微生物的定植和生物膜形成有关。然而，生物膜对细菌的保护作用、牙解剖结构的复杂性、器械可及部位的有限性等因素使传统的机械清洁和抗菌剂治疗难以完全去除感染源ADDINEN.CITEADDINEN.CITE.DATA[2]。且日益严峻的抗生素耐药问题要求我们开发新的抗菌策略ADDINEN.CITE<EndNote><Cite><Author>Jiao</Author><RecNum>442</RecNum><DisplayText><styleface="superscript">[3]</style></DisplayText><record><rec-number>442</rec-number><foreign-keys><keyapp="EN"db-id="e0zdsp9fcw0xrne5xf855e9kpttp5299a5wp"timestamp="1709035933">442</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Jiao,Y.</author><author>Tay,F.R.</author><author>Niu,L.N.</author><author>Chen,J.H.</author></authors><translated-authors><author>Int,J.OralSci</author></translated-authors></contributors><auth-address>DepartmentofStomatology,the7thMedicalCenterofPLAGeneralHospital,Beijing,PRChina.FAU-Tay,FranklinR DepartmentofEndodontics,theDentalCollegeofGeorgia,AugustaUniversity,Augusta,GA,USA.FAU-Niu,Li-Na StateKeyLaboratoryofMilitaryStomatology&NationalClinicalResearchCenterforOralDiseases&ShaanxiKeyLaboratoryofOralDiseases,DepartmentofProsthodontics,SchoolofStomatology,theFourthMilitaryMedicalUniversity,Xi'an,PRChina.niulina831013@126.com.FAU-Chen,Ji-Hua StateKeyLaboratoryofMilitaryStomatology&NationalClinicalResearchCenterforOralDiseases&ShaanxiKeyLaboratoryofOralDiseases,DepartmentofProsthodontics,SchoolofStomatology,theFourthMilitaryMedicalUniversity,Xi'an,PRChina.jhchen@.</auth-address><titles><title>Advancingantimicrobialstrategiesformanagingoralbiofilminfections</title></titles><number>2049-3169(Electronic)</number><dates></dates><urls></urls><remote-database-provider>2019Oct1</remote-database-provider><research-notes>0(Anti-BacterialAgents) 0(Anti-InfectiveAgents)</research-notes><language>eng</language></record></Cite></EndNote>[3]。ROS主要包括过氧化氢（H2O2）、单线态氧（1O2）、超氧阴离子（O2•-）、羟基自由基（•OH）等。在宿主的天然免疫防御中，ROS发挥着至关重要的作用。在正常生理状态下，ROS参与细胞内的信号转导、基因表达调控和代谢过程ADDINEN.CITE<EndNote><Cite><Author>Yang</Author><RecNum>436</RecNum><DisplayText><styleface="superscript">[4]</style></DisplayText><record><rec-number>436</rec-number><foreign-keys><keyapp="EN"db-id="e0zdsp9fcw0xrne5xf855e9kpttp5299a5wp"timestamp="1708958177">436</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Yang,B.Auid-Orcid</author><author>Chen,Y.Auid-Orcid</author><author>Shi,J.Auid-OrcidX.</author></authors><translated-authors><author>Chem,Rev</author></translated-authors></contributors><auth-address>StateKeyLaboratoryofHighPerformanceCeramicsandSuperfineMicrostructure,ShanghaiInstituteofCeramics,ChineseAcademyofSciences,Shanghai200050,P.R.China. UniversityofChineseAcademyofSciences,Beijing100049,P.R.China.FAU-Chen,Yu StateKeyLaboratoryofHighPerformanceCeramicsandSuperfineMicrostructure,ShanghaiInstituteofCeramics,ChineseAcademyofSciences,Shanghai200050,P.R.China.FAU-Shi,Jianlin</auth-address><titles><title>ReactiveOxygenSpecies(ROS)-BasedNanomedicine</title></titles><number>1520-6890(Electronic)</number><dates></dates><urls></urls><remote-database-provider>2019Apr24</remote-database-provider><research-notes>0(Anti-InflammatoryAgents) 0(Antioxidants) 0(ReactiveOxygenSpecies) 30K4522N6T(Cerium) 619G5K328Y(cericoxide)</research-notes><language>eng</language></record></Cite></EndNote>[4]。近年来，基抗菌光动力疗法、纳米酶和声动力疗法等新型抗菌策略通过快速产生大量ROS产生杀菌作用，因其微创性、广谱抗菌和不产生耐药性的特点，成为了研究热点。很多研究已经证明ROS对多种口腔致病菌和生物膜的破坏作用，有一些临床研究已将光动力疗法作为牙周炎、种植体周围炎等口腔感染性疾病的非侵入性替代或辅助治疗方法，取得了不错的效果ADDINEN.CITE<EndNote><Cite><Author>Gholami</Author><Year>2023</Year><RecNum>273</RecNum><DisplayText><styleface="superscript">[5]</style></DisplayText><record><rec-number>273</rec-number><foreign-keys><keyapp="EN"db-id="e0zdsp9fcw0xrne5xf855e9kpttp5299a5wp"timestamp="1695312487">273</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Gholami,Leila</author><author>Shahabi,Shiva</author><author>Jazaeri,Marzieh</author><author>Hadilou,Mahdi</author><author>Fekrazad,Reza</author></authors></contributors><titles><title>Clinicalapplicationsofantimicrobialphotodynamictherapyindentistry</title><secondary-title>FrontiersinMicrobiology</secondary-title></titles><volume>13</volume><dates><year>2023</year></dates><isbn>1664-302X</isbn><urls></urls><electronic-resource-num>10.3389/fmicb.2022.1020995</electronic-resource-num></record></Cite></EndNote>[5]。本文重点关注ROS产生生物材料在治疗口腔感染中的最新进展，分别介绍了基于光动力疗法的生物材料、ROS产生纳米酶、基于声动力疗法的生物材料的原理、种类和优化方法，并提出了未来发展面临的挑战和前景。1基于光动力疗法的的生物材料在光动力疗法问世不久后，抗生素就被发现并成功在临床广泛应用。这有可能是光动力疗法主要被研究应用于抗癌治疗而非抗菌治疗的原因。随着细菌耐药问题越来越严重，我们迫切需要其他有效的抗菌策略，利用光动力疗法控制感染的研究也开始逐渐深入ADDINEN.CITEADDINEN.CITE.DATA[6]。1.1光动力疗法的原理光动力疗法有三个要素：光源、光敏剂和环境氧。在细菌感染局部富集适宜浓度的无毒光敏剂，在特定波长的光照射下，光敏剂吸收光子中的能量，从基态转变为激发单线态，单线态光敏剂可以通过体系间跨越转变为寿命更长的激发三重态，随后，三线态光敏剂通过两种机制回落到基态。在机制Ⅰ中，三线态PS将电子转移到周围环境底物产生自由基，可进一步反应产生其他ROS（O2•-、H2O2、•OH），在机制Ⅱ中，三线态光敏剂将能量直接转移到基态分子氧，产生单线态氧（1O2）。两种机制可以同时发生，在缺氧环境中，Ⅰ型机制更为优越ADDINEN.CITEADDINEN.CITE.DATA[6,7]。1.2光动力疗法中的生物材料获批用于临床的传统光敏剂剂易得、无毒且具有良好的光动力特性，但它们在实际应用中还面临着很多问题。首先，大多数传统光敏剂具有疏水性，使它们常在水溶液中发生聚集而降低ROS产率ADDINEN.CITEADDINEN.CITE.DATA[8]。其次，光敏剂难以穿透致密的生物膜基质，抗生物膜效率低。此外，部分光敏剂的吸收较短波长的光，对组织的穿透能力弱ADDINEN.CITE<EndNote><Cite><Author>O'Connor</Author><RecNum>352</RecNum><DisplayText><styleface="superscript">[9]</style></DisplayText><record><rec-number>352</rec-number><foreign-keys><keyapp="EN"db-id="e0zdsp9fcw0xrne5xf855e9kpttp5299a5wp"timestamp="1700751865">352</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>O'Connor,A.E.</author><author>GallagherWmFau-Byrne,AnnetteT.</author><author>Byrne,A.T.</author></authors><translated-authors><author>Photochem,Photobiol</author></translated-authors></contributors><auth-address>UCDSchoolofBiomolecularandBiomedicalScience,UCDConwayInstitute,UniversityCollegeDublin,Belfield,Dublin,Ireland.FAU-Gallagher,WilliamM</auth-address><titles><title>Porphyrinandnonporphyrinphotosensitizersinoncology:preclinicalandclinicaladvancesinphotodynamictherapy</title></titles><number>0031-8655(Print)</number><dates></dates><urls></urls><remote-database-provider>2009Sep-Oct</remote-database-provider><research-notes>0(AntineoplasticAgents) 0(PhotosensitizingAgents) 0(Porphyrins)</research-notes><language>eng</language></record></Cite></EndNote>[9]。近年来，很多研究人员致力于通过开发智能运载体来解决这些问题。有机纳米药物输送系统如脂质体、胶束、纳米乳液、聚合物纳米颗粒等具有生物相容好和低毒性的显著优点，在应用于光动力疗法时，它们不仅提高光敏剂的水溶性和稳定性，往往也能增加光敏剂在生物膜中的渗透深度ADDINEN.CITEADDINEN.CITE.DATA[10-14]。例如，刘等将光敏剂二氢卟吩e6（Ce6）封装在聚乙二醇-b-聚(2-(二异丙氨基)甲基丙烯酸乙酯)(MPEG-b-P(PDA),MPP)中，在致龋生物膜中的酸性微环境中MPP水解并特异性释放Ce6，大大提升了Ce6在生物膜中的穿透深度（超过75%）和保留量（游离Ce6的两倍），在体外表现出显著的抗菌和抗生物膜作用，在大鼠中，MPP-Ce6介导的光动力疗法显著减少致龋菌数量，并有效降低龋损的数量和严重程度ADDINEN.CITE<EndNote><Cite><Author>Liu</Author><Year>2022</Year><RecNum>286</RecNum><DisplayText><styleface="superscript">[15]</style></DisplayText><record><rec-number>286</rec-number><foreign-keys><keyapp="EN"db-id="e0zdsp9fcw0xrne5xf855e9kpttp5299a5wp"timestamp="1695736927">286</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Liu,Danfeng</author><author>Ma,Xianbin</author><author>Ji,Yaoting</author><author>Chen,Rourong</author><author>Zhou,Shuhui</author><author>Yao,Hantao</author><author>Zhang,Zichen</author><author>Ye,Mengjie</author><author>Xu,Zhigang</author><author>Du,Minquan</author></authors></contributors><titles><title>Bioresponsivenanotherapyforpreventingdentalcariesbyinhibitingmultispeciescariogenicbiofilms</title><secondary-title>BioactiveMaterials</secondary-title></titles><periodical><full-title>BioactiveMaterials</full-title></periodical><pages>1-14</pages><volume>14</volume><section>1</section><dates><year>2022</year></dates><isbn>2452199X</isbn><urls></urls><electronic-resource-num>10.1016/j.bioactmat.2021.12.016</electronic-resource-num></record></Cite></EndNote>[15]。基于有机纳米运载体的优异特性，未来的研究可以着眼于提高其靶向运送、智能响应和控制释放的能力，改善运载量低、易渗漏、稳定性差等缺点。与有机纳米载体相比，无机纳米载体具有易于调控的参数（粒径、形状、孔隙率等）、更好的稳定性、可控药物输送等特性，金属ADDINEN.CITE<EndNote><Cite><Author>Kabanov</Author><Year>2020</Year><RecNum>356</RecNum><DisplayText><styleface="superscript">[16]</style></DisplayText><record><rec-number>356</rec-number><foreign-keys><keyapp="EN"db-id="e0zdsp9fcw0xrne5xf855e9kpttp5299a5wp"timestamp="1701182700">356</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Kabanov,V.</author><author>Heyne,B.</author></authors></contributors><titles><title>ImpactofIncoherentCouplingwithinLocalizedSurfacePlasmonResonanceonSingletOxygenProductioninRoseBengal-ModifiedSilica-CoatedSilverNanoshells(SiO₂@Ag@SiO₂-RB)</title><secondary-title>AcsAppliedNanoMaterials</secondary-title></titles><pages>8126-8137</pages><volume>3</volume><number>8</number><dates><year>2020</year><pub-dates><date>Aug</date></pub-dates></dates><isbn>2574-0970</isbn><accession-num>WOS:000566778600086</accession-num><urls><related-urls><url><GotoISI>://WOS:000566778600086</url></related-urls></urls><electronic-resource-num>10.1021/acsanm.0c01544</electronic-resource-num></record></Cite></EndNote>[16]或二氧化硅纳米颗粒ADDINEN.CITEADDINEN.CITE.DATA[17,18]介导的光动力疗法大多都取得了增强的抗菌和抗生物膜效果。上转换纳米颗粒是一类具有独特光学性质的稀土元素掺杂无机纳米材料，通过反斯托克斯发射过程,上转换纳米颗粒可将700-1100nm的近红外光转换为可见光和紫外光ADDINEN.CITEADDINEN.CITE.DATA[19,20]。由于近红外光对组织的高穿透深度和低损伤，上转换纳米颗粒可为光动力疗法在对抗深部组织（如深牙周袋）感染中激发光组织穿透力弱、损伤大、效率低的问题提供解决方案ADDINEN.CITEADDINEN.CITE.DATA[21]。张等将Ce6分子负载在两亲性硅烷和上转换纳米粒子之间的疏水层中，并掺杂了Mn来提高红光发射强度。此复合材料在980nm照射下对牙周病原菌及其相应生物膜表现出显着的抑制效果ADDINEN.CITE<EndNote><Cite><Author>Zhang</Author><Year>2019</Year><RecNum>287</RecNum><DisplayText><styleface="superscript">[22]</style></DisplayText><record><rec-number>287</rec-number><foreign-keys><keyapp="EN"db-id="e0zdsp9fcw0xrne5xf855e9kpttp5299a5wp"timestamp="1695739766">287</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Zhang,Tianshou</author><author>Ying,Di</author><author>Qi,Manlin</author><author>Li,Xue</author><author>Fu,Li</author><author>Sun,Xiaolin</author><author>Wang,Lin</author><author>Zhou,Yanmin</author></authors></contributors><titles><title>Anti-BiofilmPropertyofBioactiveUpconversionNanocompositesContainingChlorine6againstPeriodontalPathogens</title><secondary-title>Molecules</secondary-title></titles><volume>24</volume><number>15</number><section>2692</section><dates><year>2019</year></dates><isbn>1420-3049</isbn><urls></urls><electronic-resource-num>10.3390/molecules24152692</electronic-resource-num></record></Cite></EndNote>[22]。虽然上转换纳米颗粒有效解决了光动力疗法中激发光穿透深度低的问题，但在深部环境如深牙周袋往往缺乏氧气供应，影响ROS产率。开发供氧策略或选用主要通过Ⅰ型机制发挥作用的光敏剂来摆脱对环境氧的依赖是可能的解决方案。此外，与有机载体相比，无机纳米载体的生物相容性需要得到更多的关注和探究。金属有机框架材料由金属离子和有机连接体通过配位键构建，因其易于合成、高载药效率、易于修饰等特性受到生物医学界的广泛关注ADDINEN.CITEADDINEN.CITE.DATA[23,24]二维卟啉金属有机框架如四羧基苯基卟啉铜（Cu-TCPP），由卟啉核与金属离子Cu2+配位形成，具有高比表面积、丰富的活性位点和优化的光捕获能力，但电荷转移和分离效率有限。通过表面工程形成异质界面开发出基于二维卟啉金属有机骨架的纳米复合结构，实现了界面上光激发电子-空穴的高效分离ADDINEN.CITE<EndNote><Cite><Author>Li</Author><Year>2021</Year><RecNum>277</RecNum><DisplayText><styleface="superscript">[25]</style></DisplayText><record><rec-number>277</rec-number><foreign-keys><keyapp="EN"db-id="e0zdsp9fcw0xrne5xf855e9kpttp5299a5wp"timestamp="1695559805">277</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Li,Jun</author><author>Song,Shuang</author><author>Meng,Jiashen</author><author>Tan,Lei</author><author>Liu,Xiangmei</author><author>Zheng,Yufeng</author><author>Li,Zhaoyang</author><author>Yeung,KelvinWaiKwok</author><author>Cui,Zhenduo</author><author>Liang,Yanqin</author><author>Zhu,Shengli</author><author>Zhang,Xingcai</author><author>Wu,Shuilin</author></authors></contributors><titles><title>2DMOFPeriodontitisPhotodynamicIonTherapy</title><secondary-title>JournaloftheAmericanChemicalSociety</secondary-title></titles><pages>15427-15439</pages><volume>143</volume><number>37</number><section>15427</section><dates><year>2021</year></dates><isbn>0002-7863 1520-5126</isbn><urls></urls><electronic-resource-num>10.1021/jacs.1c07875</electronic-resource-num></record></Cite></EndNote>[25]。孔等将Bi2S3纳米粒子锚定在Cu-TCPP纳米片上，Bi2S3的掺入极大地提高了ROS产率，2-Bi2S3/Cu-TCPP的ROS产量约为单独Cu-TCPP的五倍。Bi2S3/Cu-TCPP在牙周炎动物模型中表现出优异的抗菌能力，还可减少胶原蛋白破坏并有效减少牙槽骨损失ADDINEN.CITE<EndNote><Cite><Author>Kong</Author><Year>2023</Year><RecNum>278</RecNum><DisplayText><styleface="superscript">[26]</style></DisplayText><record><rec-number>278</rec-number><foreign-keys><keyapp="EN"db-id="e0zdsp9fcw0xrne5xf855e9kpttp5299a5wp"timestamp="1695559900">278</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Kong,Qingchao</author><author>Qi,Manlin</author><author>Li,Wen</author><author>Shi,Yujia</author><author>Su,Jing</author><author>Xiao,Shimeng</author><author>Sun,Jiao</author><author>Bai,Xue</author><author>Dong,Biao</author><author>Wang,Lin</author></authors></contributors><titles><title>ANovelZ‐SchemeHeterostructuredBi2S3/Cu‐TCPPNanocompositewithSynergisticallyEnhancedTherapeuticsagainstBacterialBiofilmInfectionsinPeriodontitis</title><secondary-title>Small</secondary-title></titles><periodical><full-title>Small</full-title></periodical><dates><year>2023</year></dates><isbn>1613-6810 1613-6829</isbn><urls></urls><electronic-resource-num>10.1002/smll.202302547</electronic-resource-num></record></Cite></EndNote>[26]。2具有ROS产生功能的纳米酶近年来，随着纳米酶领域的快速发展，类氧化酶（OXD）或类过氧化物酶（POD）活性的人工酶越来越多地被用作抗菌剂，它们通过催化ROS产生对病原菌和生物膜产生有效的损伤作用。Au、Pd、Pt等贵金属纳米材料具有内在的类OXD或类POD活性、天然抗菌活性和生物相容性，是一类很有前途的抗菌材料。研究表明，纳米酶的催化活性与自身的基本性质（组成、结构、大小）密切相关。例如，较大的粒径导致纳米材料表面活性位点分布较少可能是限制其催化活性的原因。因此，缩小纳米材料尺寸到超小团簇（<2nm）甚至到单原子是提高原子利用率进而提高酶促活性的很有希望的策略ADDINEN.CITE<EndNote><Cite><Author>Feng</Author><Year>2022</Year><RecNum>54</RecNum><DisplayText><styleface="superscript">[27]</style></DisplayText><record><rec-number>54</rec-number><foreign-keys><keyapp="EN"db-id="esesd29epp0pvuera29vpff350p5ttz92fad"timestamp="1724848210">54</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Feng,Yonghai</author><author>Chen,Funing</author><author>Rosenholm,JessicaM.</author><author>Liu,Lei</author><author>Zhang,Hongbo</author></authors></contributors><titles><title>Efficientnanozymeengineeringforantibacterialtherapy</title><secondary-title>MaterialsFutures</secondary-title></titles><periodical><full-title>MaterialsFutures</full-title></periodical><pages>023502</pages><volume>1</volume><number>2</number><dates><year>2022</year><pub-dates><date>2022/06/28</date></pub-dates></dates><publisher>IOPPublishing</publisher><isbn>2752-5724</isbn><urls><related-urls><url>/10.1088/2752-5724/ac7068</url></related-urls></urls><electronic-resource-num>10.1088/2752-5724/ac7068</electronic-resource-num></record></Cite></EndNote>[27]。金纳米团簇因更有效地暴露活性位点而具有优异的POD样催化活性而且能够有效在生物膜中渗透和扩散。它对具核梭杆菌表现出强烈的抗菌和抗生物膜效应，并可明显减轻牙菌斑积累诱导的牙周炎症和牙周骨的丧失ADDINEN.CITE<EndNote><Cite><Author>Zhang</Author><Year>2022</Year><RecNum>313</RecNum><DisplayText><styleface="superscript">[28]</style></DisplayText><record><rec-number>313</rec-number><foreign-keys><keyapp="EN"db-id="e0zdsp9fcw0xrne5xf855e9kpttp5299a5wp"timestamp="1699368085">313</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Zhang,Yangheng</author><author>Chen,Rixin</author><author>Wang,Yuxian</author><author>Wang,Peng</author><author>Pu,Jiajie</author><author>Xu,Xiaoqiang</author><author>Chen,Faming</author><author>Jiang,Ling</author><author>Jiang,Qing</author><author>Yan,Fuhua</author></authors></contributors><titles><title>Antibiofilmactivityofultra-smallgoldnanoclustersagainstFusobacteriumnucleatumindentalplaquebiofilms</title><secondary-title>JournalofNanobiotechnology</secondary-title></titles><volume>20</volume><number>1</number><dates><year>2022</year></dates><isbn>1477-3155</isbn><urls></urls><electronic-resource-num>10.1186/s12951-022-01672-7</electronic-resource-num></record></Cite></EndNote>[28]。余等首次报道了不同金属单原子掺杂金属有机框架（PCN-222）的催化系统，其中PCN-222-Pt具有最强的OXD样和POD样活性。将PCN-222-Pt添加到可注射软膏中，在体内生物膜引起的牙周炎得到了有效治疗，并中的疗效优于临床使用的盐酸米诺环素软膏ADDINEN.CITE<EndNote><Cite><Author>Yu</Author><Year>2022</Year><RecNum>371</RecNum><DisplayText><styleface="superscript">[29]</style></DisplayText><record><rec-number>371</rec-number><foreign-keys><keyapp="EN"db-id="e0zdsp9fcw0xrne5xf855e9kpttp5299a5wp"timestamp="1701265560">371</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Yu,Yi</author><author>Cheng,Yu</author><author>Tan,Lei</author><author>Liu,Xiangmei</author><author>Li,Zhaoyang</author><author>Zheng,Yufeng</author><author>Wu,Tao</author><author>Liang,Yanqin</author><author>Cui,Zhenduo</author><author>Zhu,Shengli</author><author>Wu,Shuilin</author></authors></contributors><titles><title>Theory-screenedMOF-basedsingle-atomcatalystsforfacileandeffectivetherapyofbiofilm-inducedperiodontitis</title><secondary-title>ChemicalEngineeringJournal</secondary-title></titles><periodical><full-title>ChemicalEngineeringJournal</full-title></periodical><volume>431</volume><dates><year>2022</year><pub-dates><date>Mar1</date></pub-dates></dates><isbn>1385-8947</isbn><accession-num>WOS:000773002600003</accession-num><work-type>Article</work-type><urls><related-urls><url><GotoISI>://WOS:000773002600003</url></related-urls></urls><custom7>133279</custom7><electronic-resource-num>10.1016/j.cej.2021.133279</electronic-resource-num></record></Cite></EndNote>[29]。氧化铁纳米粒子是最常见的纳米酶，它在酸性环境下具有强POD的催化活性，能够在致龋生物膜酸性生态位中原位催化H2O2产生ROS杀伤致病菌并降解细胞外基质ADDINEN.CITEADDINEN.CITE.DATA[30]。Ferumoxytol，一种羧甲基葡聚糖涂层的氧化铁纳米颗粒制剂，经FDA批准用于全身治疗铁缺乏症。近来研究发现，Ferumoxytol通过葡聚糖涂层优先与变异链球菌表面多种葡聚糖结合蛋白结合而表现出抗菌特异性并增强纳米颗粒对生物膜的渗透，同时ROS扩散距离缩小显著增强了效果。得益于其pH依赖酶模拟活性、靶向杀菌作用和生物相容性，葡聚糖涂层的氧化铁纳米颗粒在不对周围健康口腔组织产生损伤的情况下，在啮齿动物模型和人体中都表现出有效的破坏致龋生物膜、阻止龋病进展的作用ADDINEN.CITEADDINEN.CITE.DATA[31,32]。此外，刘等发现Ferumoxytol与SnF2混合有显著的协同作用ADDINEN.CITE<EndNote><Cite><Author>Huang</Author><Year>2023</Year><RecNum>306</RecNum><DisplayText><styleface="superscript">[33]</style></DisplayText><record><rec-number>306</rec-number><foreign-keys><keyapp="EN"db-id="e0zdsp9fcw0xrne5xf855e9kpttp5299a5wp"timestamp="1699366692">306</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Huang,Yue</author><author>Liu,Yuan</author><author>Pandey,Nil</author><author>Shah,Shrey</author><author>Simon-Soro,Aurea</author><author>Hsu,Jessica</author><author>Ren,Zhi</author><author>Xiang,Zhenting</author><author>Kim,Dongyeop</author><author>Ito,Tatsuro</author><author>Oh,MinJun</author><author>Buckley,Christine</author><author>Alawi,Faizan</author><author>Li,Yong</author><author>Smeets,Paul</author><author>Boyer,Sarah</author><author>Zhao,Xingchen</author><author>Joester,Derk</author><author>Zero,Domenick</author><author>Cormode,David</author><author>Koo,Hyun</author></authors></contributors><titles><title>Ironoxidenanozymesstabilizestannousfluoridefortargetedbiofilmkillingandsynergisticoraldiseaseprevention</title></titles><dates><year>2023</year></dates><urls></urls><electronic-resource-num>10.21203/rs.3.rs-2723097/v1</electronic-resource-num></record></Cite></EndNote>[33]，Ferumoxytol的催化活性得到增强的同时SnF2在水溶剂中的稳定性显著提高，极小量氧化铁纳米颗粒制剂（<已批准全身剂量的0.2%）即可产生有效的局部效果还增加了防止牙釉质脱矿和空化的作用，有利于临床转化。然而，生理条件下局部H2O2的浓度较低，难以达到较高的ROS产率和理想的抗菌效果。直接外源性补充H2O2增加了治疗程序、利用率低且刺激正常组织，故而由生物材料原位产生H2O2更为理想。这可以通过共载H2O2供体或级联催化来实现。CaO2纳米颗粒在酸性环境中迅速分解产生H2O2，常被用作有效的H2O2供体。宋等将其与Fe3O4纳米颗粒共同加载到水凝胶中，与Fe3O4水凝胶组相比，Fe3O4-CaO2水凝胶能强烈清除根管生物膜感染，并防止炎症进一步扩展[65]3基于声动力疗法的的生物材料超声导的声动力疗法是一种广泛用于肿瘤和细菌感染的非侵入性治疗策略。与光动力疗法相比，超声照射的显著优势在于其优越的组织穿透性和超声波仪器在牙科的广泛的应用ADDINEN.CITEADDINEN.CITE.DATA[34,35]。SDT的机制主要是细胞毒性ROS的产生、声动力损伤和热损伤效应，虽然确切的机理仍未得到阐明，但基于超声空化效应的假说被广泛接受。在超声照射下，液体中微气泡产生、膨胀、破裂，气泡的坍塌通过两种可能的机制触发ROS产生，声致发光以激发光敏剂产生电子空穴或产生热量以引起水和光敏剂热解。气泡坍塌也会导致机械损伤，可能在细胞膜表面形成孔隙，空化过程中机械能部分转化成热能也具有一定损伤作用ADDINEN.CITE<EndNote><Cite><Author>Xu</Author><RecNum>389</RecNum><DisplayText><styleface="superscript">[36]</style></DisplayText><record><rec-number>389</rec-number><foreign-keys><keyapp="EN"db-id="e0zdsp9fcw0xrne5xf855e9kpttp5299a5wp"timestamp="1702133427">389</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Xu,P.Y.</author><author>KumarKankala,R.</author><author>Wang,S.B.</author><author>Chen,A.Z.</author></authors><translated-authors><author>Ultrason,Sonochem</author></translated-authors></contributors><auth-address>InstituteofBiomaterialsandTissueEngineering,HuaqiaoUniversity,Xiamen,Fujian361021,PRChina;FujianProvincialKeyLaboratoryofBiochemicalTechnology,HuaqiaoUniversity,Xiamen,Fujian361021,PRChina.FAU-KumarKankala,Ranjith InstituteofBiomaterialsandTissueEngineering,HuaqiaoUniversity,Xiamen,Fujian361021,PRChina;FujianProvincialKeyLaboratoryofBiochemicalTechnology,HuaqiaoUniversity,Xiamen,Fujian361021,PRChina.FAU-Wang,Shi-Bin InstituteofBiomaterialsandTissueEngineering,HuaqiaoUniversity,Xiamen,Fujian361021,PRChina;FujianProvincialKeyLaboratoryofBiochemicalTechnology,HuaqiaoUniversity,Xiamen,Fujian361021,PRChina.FAU-Chen,Ai-Zheng InstituteofBiomaterialsandTissueEngineering,HuaqiaoUniversity,Xiamen,Fujian361021,PRChina;FujianProvincialKeyLaboratoryofBiochemicalTechnology,HuaqiaoUniversity,Xiamen,Fujian361021,PRChina.Electronicaddress:azchen@.</auth-address><titles><title>Sonodynamictherapy-basednanoplatformsforcombatingbacterialinfections</title></titles><number>1873-2828(Electronic)</number><dates></dates><urls></urls><remote-database-provider>2023Nov</remote-database-provider><research-notes>0(Anti-BacterialAgents) 0(ReactiveOxygenSpecies)</research-notes><language>eng</language></record></Cite></EndNote>[36]。声敏剂是声动力疗法的重要组分，有机小分子声敏剂大部分来源于光敏剂，如卟啉衍生物、ICG、姜黄素等ADDINEN.CITEADDINEN.CITE.DATA[35,37]，也具有传统光敏剂的缺点和类似的运载策略。最近，孙等将传统声敏剂四苯基卟啉（TPP）与新型光敏剂碲紫罗碱（TeV）结合构建了一种新型声敏剂，TPP-TeV。TPP-TeV具有优异的超声照射下自由基生成能力和很低生物毒性，在体外和体内有效杀灭牙龈卟啉单胞菌，对牙槽骨丢失的抑制率达到80%ADDINEN.CITEADDINEN.CITE.DATA[38]。近年来，各种具有声敏特性的纳米材料在声动力疗法中得到快速发展和广泛应用，如钛基纳米材料、钛酸钡(BTO)纳米颗粒、氧化锌纳米颗粒等ADDINEN.CITEADDINEN.CITE.DATA[39,40]，这些无机声敏剂具有更低的光毒性、更高的稳定性和可调的物理化学性质ADDINEN.CITE<EndNote><Cite><Author>Liang</Author><RecNum>392</RecNum><DisplayText><styleface="superscript">[41]</style></DisplayText><record><rec-number>392</rec-number><foreign-keys><keyapp="EN"db-id="e0zdsp9fcw0xrne5xf855e9kpttp5299a5wp"timestamp="1702188912">392</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Liang,S.</author><author>Deng,X.</author><author>Ma,P.</author><author>Cheng,Z.Auid-Orcid</author><author>Lin,J.</author></authors><translated-authors><author>Adv,Mater</author></translated-authors></contributors><auth-address>StateKeyLaboratoryofRareEarthResourceUtilization,ChangchunInstituteofAppliedChemistry,ChineseAcademyofSciences,Changchun,130022,China. UniversityofScienceandTechnologyofChina,Hefei,230026,China.FAU-Deng,Xiaoran StateKeyLaboratoryofRareEarthResourceUtilization,ChangchunInstituteofAppliedChemistry,ChineseAcademyofSciences,Changchun,130022,China.FAU-Ma,Ping'an UniversityofScienceandTechnologyofChina,Hefei,230026,China.FAU-Cheng,Ziyong UniversityofScienceandTechnologyofChina,Hefei,230026,China.FAU-Lin,Jun UniversityofScienceandTechnologyofChina,Hefei,230026,China.</auth-address><titles><title>RecentAdvancesinNanomaterial-AssistedCombinationalSonodynamicCancerTherapy</title></titles><number>1521-4095(Electronic)</number><dates></dates><urls></urls><remote-database-provider>2020Nov</remote-database-provider><language>eng</language></record></Cite></EndNote>[41]。近年来，许多研究应用超声技术和激光技术去除根管隐匿部位感染。考虑到激光的照射深度和根管内难以被照射到的解剖结构，声动力疗法在根管内感染的控制中更有前景。Xu等开发出表面分布有BTO@Au纳米颗粒的压电古塔胶，将其植入人离体牙齿中粪肠球菌感染的根管。在超声照射下，ROS在牙胶和根管之间的有限空间内产生，抗菌率可达95%。若根管再次感染也只需超声照射治疗，治疗流程得到简化ADDINEN.CITEADDINEN.CITE.DATA[42]。4小结与展望口腔感染性疾病发病率高，对患者的生活质量和全身健康造成严重的负面影响。为弥补传统治疗方法的不足，开发先进的治疗策略具有重要意义。本文综述了近年来牙科领域基于ROS产生生物材料的前沿研究。光动力疗法、纳米酶、声动力疗法等ROS产生策略利用纳米技术、结构和功能修饰等方法实现了ROS产量的提升，有利于获得更好的抗菌效果。此外，ROS产生与抗生素、光热疗法、化学动力学疗法等多模式联合协同作用，可能开发出更高效、副作用更少的治疗平台。未来ROS相关生物材料的研究需要更多关注材料的低效能、长期全身毒性、生物分布和降解途径不清等仍存在的问题。ROS在机体正常生命活动中发挥重要作用，然而，ROS过量产生会导致氧化应激，直接损伤细胞的脂质、蛋白质和核酸等生物大分子，并可通过多种机制加剧炎症反应和组织损伤。因此，为了观测治疗效果并避免产生毒副作用，可能需要与其他技术的帮助以智能监测材料施用后局部的ROS水平。要实现ROS产生生物材料的临床转化，还有很多的问题需要解决，还需要很长时间的探索和研究，但应用前景十分广阔。

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