《肿瘤的声动力治疗简介》3300字

肿瘤的声动力治疗简介综述1.1声动力治疗的机制超声波是一种频率高于20000Hz的机械波，因为其对人体作用的安全性，在临床中常用于成像诊断ADDINEN.CITE<EndNote><Cite><Author>Cox</Author><Year>2015</Year><RecNum>81</RecNum><DisplayText><styleface="superscript">[74]</style></DisplayText><record><rec-number>81</rec-number><foreign-keys><keyapp="EN"db-id="fefzva2arafxvjeezt3vr2rhx22ervre0wt2"timestamp="1599095856">81</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Cox,B.</author><author>Beard,P.</author></authors></contributors><auth-address>DepartmentofMedicalPhysicsandBiomedicalEngineering,UniversityCollegeLondon,LondonWC1E6BT,UK.</auth-address><titles><title>Imagingtechniques:Super-resolutionultrasound</title><secondary-title>Nature</secondary-title></titles><periodical><full-title>Nature</full-title></periodical><pages>451-2</pages><volume>527</volume><number>7579</number><edition>2015/11/27</edition><keywords><keyword>Animals</keyword><keyword>Brain/*bloodsupply</keyword><keyword>Male</keyword><keyword>Microscopy/*methods</keyword><keyword>*Microvessels</keyword><keyword>MolecularImaging/*methods</keyword><keyword>Ultrasonics/*methods</keyword></keywords><dates><year>2015</year><pub-dates><date>Nov26</date></pub-dates></dates><isbn>1476-4687(Electronic) 0028-0836(Linking)</isbn><accession-num>26607538</accession-num><urls><related-urls><url>/pubmed/26607538</url></related-urls></urls><electronic-resource-num>10.1038/527451a</electronic-resource-num></record></Cite></EndNote>[\o"Cox,2015#81"74]。超声的治疗作用包括超声吸收热疗与超声热消融手术等，它们都是基于超声的热效应原理。声动力治疗（Sonodynamictherapy，SDT）是以超声波为主的新型治疗手段，它可以用于动脉粥样硬化治疗、抗细菌感染以及癌症治疗ADDINEN.CITEADDINEN.CITE.DATA[\o"Pang,2019#60"75-77]。1989年，SDT展现出雏形，相关报道发现了血卟啉在超声存在下能导致更多的细胞损伤ADDINEN.CITE<EndNote><Cite><Author>Yumita</Author><Year>1989</Year><RecNum>48</RecNum><DisplayText><styleface="superscript">[78]</style></DisplayText><record><rec-number>48</rec-number><foreign-keys><keyapp="EN"db-id="fefzva2arafxvjeezt3vr2rhx22ervre0wt2"timestamp="1598618019">48</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Yumita,N.</author><author>Nishigaki,R.</author><author>Umemura,K.</author><author>Umemura,S.</author></authors></contributors><auth-address>FacultyofPharmaceuticalScience,TohoUniversity,Chiba.</auth-address><titles><title>Hematoporphyrinasasensitizerofcell-damagingeffectofultrasound</title><secondary-title>JpnJCancerRes</secondary-title></titles><periodical><full-title>JpnJCancerRes</full-title></periodical><pages>219-22</pages><volume>80</volume><number>3</number><edition>1989/03/01</edition><keywords><keyword>Animals</keyword><keyword>CellSurvival</keyword><keyword>Hematoporphyrins/*therapeuticuse</keyword><keyword>LiverNeoplasms,Experimental/pathology/*therapy</keyword><keyword>Male</keyword><keyword>Mice</keyword><keyword>Mice,InbredICR</keyword><keyword>Rats</keyword><keyword>Sarcoma180/pathology/*therapy</keyword><keyword>StainingandLabeling</keyword><keyword>TrypanBlue</keyword><keyword>TumorCells,Cultured</keyword><keyword>*UltrasonicTherapy</keyword></keywords><dates><year>1989</year><pub-dates><date>Mar</date></pub-dates></dates><isbn>0910-5050(Print) 0910-5050(Linking)</isbn><accession-num>2470713</accession-num><urls><related-urls><url>/pubmed/2470713</url></related-urls></urls><custom2>PMC5917717</custom2><electronic-resource-num>10.1111/j.1349-7006.1989.tb02295.x</electronic-resource-num></record></Cite></EndNote>[\o"Yumita,1989#48"78]。SDT由PDT发展而来，相比于PDT，超声介导的SDT具有非侵害性、深组织穿透力、高精度等独特的优点，超声能够到达更深层次的器官，如胰腺、肝脏和肿瘤。研究人员为了阐明SDT的机制，最初是将PDT的机制顺推到到SDT当中。然而实际上SDT作用的原理更加复杂，不像PDT引起光动力效应是单一的由光辐射激活光敏剂通过能量及电子转移等过程诱导产生活性氧（Reactiveoxygenspecies，ROS）ADDINEN.CITEADDINEN.CITE.DATA[\o"Li,2020#106"79,\o"Im,2021#107"80]。SDT由于其复杂的过程，现今仍未明确其作用的机制。但经过科研人员的不断努力，已经发现了SDT的部分机制（图1-5），其中包括了ROS的产生、空化气穴效应、热效应及直接诱导细胞凋亡等ADDINEN.CITEADDINEN.CITE.DATA[\o"Hiraoka,2006#67"81-83]。首先，SDT与PDT有较为类似的一点，都能够通过激活其各自的敏化剂产生ROS，并诱导细胞死亡。在SDT中，超声波的能量激活了声敏剂，通过类似PDT的原理产生了ROS，这是大多数文章都报道过的一种机制，也是最广为接受的机制。超声介导的ROS能够增强细胞膜的通透性和刺激Ca2+通过离子通道内流ADDINEN.CITEADDINEN.CITE.DATA[\o"Zhang,2014#116"84,\o"Zhang,2018#117"85]。其次，超声波辐射时，部分能量传输到周围介质中，将会引起对流运动，称作“声流”。气态内含物如微泡在超声振荡下，部分区域会发生这种对流运动并存在剪切应力，在这种情况下，会产生“非惯性”的空腔。随着持续的超声振荡，这些空腔会急速内缩并发生内爆，在极短暂的时间内产生极高的热量，这一气穴形成、振荡并塌缩的周期过程是超声处理下非常重要的一个机械效应。在对细胞超声时，这种机械效应能引起瞬态膜孔隙、细胞膜变形等结果ADDINEN.CITEADDINEN.CITE.DATA[\o"Hassan,2010#120"86,\o"vanWamel,2006#121"87]。这种机械效应被很多报道称为“空化效应”。很多实验证明，超声波能够在细胞或组织液中产生极小的气泡空穴，气泡在超声的作用下振动，随之发生急速膨胀并塌缩，这个过程使空穴内温度在极短的时间内超过了5000K。空化作用产生的局部高温高压会诱导区域内发生一系列自由基反应，包括空穴内部、空穴与溶剂相交的界面，最终呈现出超声化学效应，而且空化效应是多元控制的，超声波的频率与强度、环境的温度与压力、溶液的粘度等参数的变化都会影响着空化效应ADDINEN.CITE<EndNote><Cite><Author>Rosenthal</Author><Year>2004</Year><RecNum>50</RecNum><DisplayText><styleface="superscript">[88]</style></DisplayText><record><rec-number>50</rec-number><foreign-keys><keyapp="EN"db-id="fefzva2arafxvjeezt3vr2rhx22ervre0wt2"timestamp="1598623686">50</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Rosenthal,I.</author><author>Sostaric,J.Z.</author><author>Riesz,P.</author></authors></contributors><auth-address>RadiationBiologyBranch,NationalCancerInstitute,NationalInstitutesofHealth,Bethesda,MD20892-1002,USA.</auth-address><titles><title>Sonodynamictherapy--areviewofthesynergisticeffectsofdrugsandultrasound</title><secondary-title>UltrasonSonochem</secondary-title></titles><periodical><full-title>UltrasonSonochem</full-title></periodical><pages>349-63</pages><volume>11</volume><number>6</number><edition>2004/08/11</edition><keywords><keyword>Animals</keyword><keyword>AntineoplasticAgents/*therapeuticuse</keyword><keyword>CellMembrane/drugeffects/radiationeffects</keyword><keyword>*CombinedModalityTherapy</keyword><keyword>*DrugTherapy</keyword><keyword>FreeRadicals</keyword><keyword>Humans</keyword><keyword>Neoplasms/drugtherapy/pathology/*therapy</keyword><keyword>*UltrasonicTherapy</keyword></keywords><dates><year>2004</year><pub-dates><date>Sep</date></pub-dates></dates><isbn>1350-4177(Print) 1350-4177(Linking)</isbn><accession-num>15302020</accession-num><urls><related-urls><url>/pubmed/15302020</url></related-urls></urls><electronic-resource-num>10.1016/j.ultsonch.2004.03.004</electronic-resource-num></record></Cite></EndNote>[\o"Rosenthal,2004#50"88]。Ueda等人的实验结果显示低频率超声可能导致更强的空化作用ADDINEN.CITE<EndNote><Cite><Author>Ueda</Author><Year>2009</Year><RecNum>113</RecNum><DisplayText><styleface="superscript">[89]</style></DisplayText><record><rec-number>113</rec-number><foreign-keys><keyapp="EN"db-id="fefzva2arafxvjeezt3vr2rhx22ervre0wt2"timestamp="1617846368">113</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Ueda,H.</author><author>Mutoh,M.</author><author>Seki,T.</author><author>Kobayashi,D.</author><author>Morimoto,Y.</author></authors></contributors><auth-address>FacultyofPharmaceuticalSciences,JosaiUniversity,Sakado,Saitama,Japan.hideo@josai.ac.jp</auth-address><titles><title>Acousticcavitationasanenhancingmechanismoflow-frequencysonophoresisfortransdermaldrugdelivery</title><secondary-title>BiolPharmBull</secondary-title></titles><periodical><full-title>BiolPharmBull</full-title></periodical><pages>916-20</pages><volume>32</volume><number>5</number><edition>2009/05/08</edition><keywords><keyword>*Acoustics/instrumentation</keyword><keyword>Administration,Cutaneous</keyword><keyword>Animals</keyword><keyword>Gelatin/chemistry</keyword><keyword>InVitroTechniques</keyword><keyword>Male</keyword><keyword>Microscopy,Confocal</keyword><keyword>PharmaceuticalPreparations/*administration&dosage/chemistry</keyword><keyword>Phonophoresis/instrumentation/*methods</keyword><keyword>Rats</keyword><keyword>Rats,Hairless</keyword><keyword>Skin/drugeffects/*metabolism</keyword><keyword>*SkinAbsorption</keyword><keyword>Solutions</keyword><keyword>*Ultrasonics</keyword><keyword>Water/chemistry</keyword></keywords><dates><year>2009</year><pub-dates><date>May</date></pub-dates></dates><isbn>0918-6158(Print) 0918-6158(Linking)</isbn><accession-num>19420764</accession-num><urls><related-urls><url>/pubmed/19420764</url></related-urls></urls><electronic-resource-num>10.1248/bpb.32.916</electronic-resource-num></record></Cite></EndNote>[\o"Ueda,2009#113"89]。超声的热效应会随着声波的占空比而改变，脉冲波产生的热效应会小于连续超声波，且脉冲波也足以产生空化活性，因此调整脉冲波的使用可以用于调节超声产生的热效应与空化效用。此外，超声空化对生物组织还有一种独特的效应，称为声孔效应（Sonoporation）。在生物组织液中存在许多微小气泡，超声波激活这些气泡产生了空化作用。当空化气穴塌缩，其蕴含的能量有的被均匀地释放到周围环境中，而另一些不对称的气穴塌缩时会从一个角度喷射高速液体ADDINEN.CITE<EndNote><Cite><Author>Stride</Author><Year>2010</Year><RecNum>123</RecNum><DisplayText><styleface="superscript">[90]</style></DisplayText><record><rec-number>123</rec-number><foreign-keys><keyapp="EN"db-id="fefzva2arafxvjeezt3vr2rhx22ervre0wt2"timestamp="1617889748">123</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Stride,E.P.</author><author>Coussios,C.C.</author></authors></contributors><auth-address>DepartmentofMechanicalEngineering,UniversityCollegeLondon,London,UK.e_stride@meng.ucl.ac.uk</auth-address><titles><title>Cavitationandcontrast:theuseofbubblesinultrasoundimagingandtherapy</title><secondary-title>ProcInstMechEngH</secondary-title></titles><periodical><full-title>ProcInstMechEngH</full-title></periodical><pages>171-91</pages><volume>224</volume><number>2</number><edition>2010/03/31</edition><keywords><keyword>ComputerSimulation</keyword><keyword>ContrastMedia/*chemistry/*radiationeffects</keyword><keyword>DrugCarriers/*chemistry/*radiationeffects</keyword><keyword>ImageEnhancement/methods</keyword><keyword>*Microbubbles</keyword><keyword>Models,Chemical</keyword><keyword>RadiationDosage</keyword><keyword>Sonication/methods</keyword><keyword>UltrasonicTherapy/*methods</keyword><keyword>Ultrasonography/*methods</keyword></keywords><dates><year>2010</year></dates><isbn>0954-4119(Print) 0954-4119(Linking)</isbn><accession-num>20349814</accession-num><urls><related-urls><url>/pubmed/20349814</url></related-urls></urls><electronic-resource-num>10.1243/09544119JEIM622</electronic-resource-num></record></Cite></EndNote>[\o"Stride,2010#123"90]。不论是哪一种，随着空穴的形成与溃灭，局域内爆发的能量影响着周围的环境，细胞膜表面的空化过程会导致膜产生孔状结构，使细胞膜通透性增加，一些难以透过活细胞膜的药物分子此时可以通过内吞进入细胞ADDINEN.CITEADDINEN.CITE.DATA[\o"Yu,2014#71"91-94]。这种声孔效应在低功率的超声条件下发生是瞬时的、可恢复的，并且它对细胞膜作用产生的孔径能够达到150nm，现在它已被用做提高药物递送的一种方式，比如提高基因转染率ADDINEN.CITEADDINEN.CITE.DATA[\o"Castle,2016#73"95-97]。声孔效应常与超声造影剂微泡联合作用，以达到更好的药物靶向输送效率。因为超声对气体的反射比对液体大得多（近1000倍），超声造影剂由于其含有的气泡可以增强超声的散射回声，可以提高超声影像的分辨率。气泡在SDT中可能扮演着一个重要的角色，有着提高SDT效果的潜在效用。除了机械效应之外，热效应是超声治疗最早利用的一种机制。高强度聚焦超声（Highintensityfocusedultrasound，HIFU）已被用于热效应治疗（癌症热消融治疗），它能够在几秒内将局部温度升至70℃以上，对组织造成不可逆转的损伤ADDINEN.CITEADDINEN.CITE.DATA[\o"Maeshige,2020#112"98]。超声的热效应是多种因素共同决定的结果，超声频率、聚焦程度、持续脉冲时间、超声辐射时间和吸收系数在超声引起温度升高的过程中起着决定作用ADDINEN.CITE<EndNote><Cite><Author>Shankar</Author><Year>2011</Year><RecNum>114</RecNum><DisplayText><styleface="superscript">[99]</style></DisplayText><record><rec-number>114</rec-number><foreign-keys><keyapp="EN"db-id="fefzva2arafxvjeezt3vr2rhx22ervre0wt2"timestamp="1617847676">114</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Shankar,H.</author><author>Pagel,P.S.</author></authors></contributors><auth-address>ClementZablockiVeteransAffairsMedicalCenter,MedicalCollegeofWisconsin,Milwaukee,Wisconsin,USA.hshankar@</auth-address><titles><title>Potentialadverseultrasound-relatedbiologicaleffects:acriticalreview</title><secondary-title>Anesthesiology</secondary-title></titles><periodical><full-title>Anesthesiology</full-title></periodical><pages>1109-24</pages><volume>115</volume><number>5</number><edition>2011/08/26</edition><keywords><keyword>Animals</keyword><keyword>ChromosomeAberrations</keyword><keyword>Fetus/radiationeffects</keyword><keyword>Humans</keyword><keyword>Lung/radiationeffects</keyword><keyword>Neurons/radiationeffects</keyword><keyword>PatientSafety</keyword><keyword>Ultrasonography/*adverseeffects/instrumentation</keyword></keywords><dates><year>2011</year><pub-dates><date>Nov</date></pub-dates></dates><isbn>1528-1175(Electronic) 0003-3022(Linking)</isbn><accession-num>21866043</accession-num><urls><related-urls><url>/pubmed/21866043</url></related-urls></urls><electronic-resource-num>10.1097/ALN.0b013e31822fd1f1</electronic-resource-num></record></Cite></EndNote>[\o"Shankar,2011#114"99]。比如，对人体进行超声，超声波束在传播路径上遇到液体，温度只有微弱的上升；相反，当在高度吸收的组织（如骨骼）中发传播，则温度会有较之明显的上升。同时聚焦程度也极大影响着超声热效应，HIFU便是利用了这一点，提高热效应的同时缩小了治疗范围，精准热消融病变区域。聚焦超声波还是非侵入性、针对性打开血脑屏障（BBB）的重要方法ADDINEN.CITE<EndNote><Cite><Author>Leinenga</Author><Year>2016</Year><RecNum>122</RecNum><DisplayText><styleface="superscript">[100]</style></DisplayText><record><rec-number>122</rec-number><foreign-keys><keyapp="EN"db-id="fefzva2arafxvjeezt3vr2rhx22ervre0wt2"timestamp="1617888875">122</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Leinenga,G.</author><author>Langton,C.</author><author>Nisbet,R.</author><author>Gotz,J.</author></authors></contributors><auth-address>ClemJonesCentreforAgeingDementiaResearch,QueenslandBrainInstitute,TheUniversityofQueensland,StLuciaCampus,Brisbane,Queenland4072,Australia. InstituteofHealthandBiomedicalInnovation,QueenslandUniversityofTechnology,KelvinGroveCampus,Brisbane,Queenland4059,Australia.</auth-address><titles><title>Ultrasoundtreatmentofneurologicaldiseases--currentandemergingapplications</title><secondary-title>NatRevNeurol</secondary-title></titles><periodical><full-title>NatRevNeurol</full-title></periodical><pages>161-74</pages><volume>12</volume><number>3</number><edition>2016/02/20</edition><keywords><keyword>Animals</keyword><keyword>Blood-BrainBarrier/diagnosticimaging/metabolism</keyword><keyword>Humans</keyword><keyword>NervousSystemDiseases/*diagnosticimaging/metabolism/*therapy</keyword><keyword>TreatmentOutcome</keyword><keyword>UltrasonicTherapy/*trends</keyword><keyword>Ultrasonography,Interventional/*trends</keyword></keywords><dates><year>2016</year><pub-dates><date>Mar</date></pub-dates></dates><isbn>1759-4766(Electronic) 1759-4758(Linking)</isbn><accession-num>26891768</accession-num><urls><related-urls><url>/pubmed/26891768</url></related-urls></urls><electronic-resource-num>10.1038/nrneurol.2016.13</electronic-resource-num></record></Cite></EndNote>[\o"Leinenga,2016#122"100]。图1-5SDT的机制图示。1O2：单线态氧；OH：羟基自由基；HO2·：超氧自由基ADDINEN.CITEADDINEN.CITE.DATA[\o"Pan,2018#298"101]。超声的热效应也有某种独特的生理作用。超声波从探头发射，传播路径的分子在压缩和膨胀的周期中振动，能量依靠这个过程从探头处传播到了目标位置，这种能量传输便引起了一定程度的升温。超声波引发的体温升高能提高细胞中的药物摄取，对抗耐药性ADDINEN.CITEADDINEN.CITE.DATA[\o"Liu,2001#119"102]。超声与细胞相互作用并加强细胞对小分子药物的摄取受多种因素制约，包括超声参数，细胞属性等。其中细胞的结构、大小和弹性因细胞株不同而各异，且即使同一株细胞，其细胞特性也会因细胞密度、细胞周期相而变化。超声对不同类型的细胞诱导膜渗透的作用时间有显著差异ADDINEN.CITEADDINEN.CITE.DATA[\o"Lammertink,2015#118"103]。SDT主要侧重于非热效应，利用低强度的超声通过多种机制激活声敏剂并引起细胞损伤，最终导致细胞坏死或凋亡。一些研究表明超声波还会引起线粒体膜电位的变化、细胞膜损伤及DNA裂解等特征，证明了超声波能够诱发细胞凋亡ADDINEN.CITEADDINEN.CITE.DATA[\o"Feril,2002#109"104-106]。Noriaki等人的研究显示超声波在细胞膜上造成小孔引起细胞凋亡ADDINEN.CITEADDINEN.CITE.DATA[\o"Maeshige,2020#112"98]。超声除了可用于SDT和HIFU等治疗手段，它还会对纳米粒产生一些物理化学的改变，比如改变纳米流体的粘度和稳定性，减少团簇的大小，提高胶体的分散性和稳定性等ADDINEN.CITEADDINEN.CITE.DATA[\o"Asadi,2019#115"107]。总体来说，关于SDT的机制可能不是共通的，会受到声敏剂，超声参数和生物模型的性质等多种要素影响ADDINEN.CITE<EndNote><Cite><Author>Rosenthal</Author><Year>2004</Year><RecNum>50</RecNum><DisplayText><styleface="superscript">[88]</style></DisplayText><record><rec-number>50</rec-number><foreign-keys><keyapp="EN"db-id="fefzva2arafxvjeezt3vr2rhx22ervre0wt2"timestamp="1598623686">50</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Rosenthal,I.</author><author>Sostaric,J.Z.</author><author>Riesz,P.</author></authors></contributors><auth-address>RadiationBiologyBranch,NationalCancerInstitute,NationalInstitutesofHealth,Bethesda,MD20892-1002,USA.</auth-address><titles><title>Sonodynamictherapy--areviewofthesynergisticeffectsofdrugsandultrasound</title><secondary-title>UltrasonSonochem</secondary-title></titles><periodical><full-title>UltrasonSonochem</full-title></periodical><pages>349-63</pages><volume>11</volume><number>6</number><edition>2004/08/11</edition><keywords><keyword>Animals</keyword><keyword>AntineoplasticAgents/*therapeuticuse</keyword><keyword>CellMembrane/drugeffects/radiationeffects</keyword><keyword>*CombinedModalityTherapy</keyword><keyword>*DrugTherapy</keyword><keyword>FreeRadicals</keyword><keyword>Humans</keyword><keyword>Neoplasms/drugtherapy/pathology/*therapy</keyword><keyword>*UltrasonicTherapy</keyword></keywords><dates><year>2004</year><pub-dates><date>Sep</date></pub-dates></dates><isbn>1350-4177(Print) 1350-4177(Linking)</isbn><accession-num>15302020</accession-num><urls><related-urls><url>/pubmed/15302020</url></related-urls></urls><electronic-resource-num>10.1016/j.ultsonch.2004.03.004</electronic-resource-num></record></Cite></EndNote>[\o"Rosenthal,2004#50"88]。1.2声敏剂SDT要达到良好的效果需要三个元素：低强度超声，声敏剂以及氧分子，声敏剂是其中的关键元素ADDINEN.CITEADDINEN.CITE.DATA[\o"Pang,2016#108"108]。产生ROS是SDT重要的机制之一，它与靶向化疗药结合具有优秀的协同疗效。声敏剂（Sonosensitizers）是在超声作用下能够产生ROS的化合物，是超声与氧分子之间的桥梁。类似于光敏剂（Photosensitizers），声敏剂在一定频率强度的超声辐射下，分子从基态被激活到激发态再返回基态的过程中，声敏剂释放能量转移到附近的氧分子，进而产生ROS。声敏剂不在超声作用时呈现低毒性。在过去的几十年里已经研究和开发了多种类型的声敏剂，包括有机分子、无机纳米材料和基于金属的材料。第一代被开发使用的声敏剂是卟啉类。其中常见的有原卟啉IX（PPIX）、血卟啉（Hp）、血卟啉单甲基醚（HMME）以及其他卟啉衍生物。赤藓红B（EB）和玫瑰红（RB）作为氧杂蒽类声敏剂，也表现出不俗的声动效率。其中RB的各种衍生物还展现出了光声动力协同作用，在肝癌细胞中表现出显著的抗癌效果ADDINEN.CITEADDINEN.CITE.DATA[\o"Chen,2018#277"109]。二氢卟吩e6（Ce6）是一种天然，一些研究证明Ce6也具有声动力抗肿瘤效果，超声提高细胞对纳米药物的摄取从而增强了SDT的效果ADDINEN.CITEADDINEN.CITE.DATA[\o"Wang,2018#271"110,\o"Li,2014#273"111]。Ce6和亲水性聚乙烯吡咯烷酮（PVP）结合形成了光子（Photolon）ADDINEN.CITEADDINEN.CITE.DATA[\o"Copley,2008#275"112]，这是一种极有前景的光敏剂，已经被批准用于临床。吲哚菁绿（ICG）是一种小分子声敏剂，以被FDA批准用于光学医学成像和诊断ADDINEN.CITEADDINEN.CITE.DATA[\o"Newton,2019#281"113]，有研究报道包裹ICG的功能脂质微粒在卵巢癌中实现了靶向光声成像且表现出不俗的光声动力与光热协同抗肿瘤效应ADDINEN.CITEADDINEN.CITE.DATA[\o"Liu,2019#279"114]。无机纳米材料也被用作声敏剂，与有机小分子相比，它们具有更为优越的物理化学特性和稳定性。二氧化钛（TiO2）是一种典型的半导体，紫外照射下具有光毒性ADDINEN.CITE<EndNote><Cite><Author>Zhang</Author><Year>2018</Year><RecNum>147</RecNum><DisplayText><styleface="superscript">[115]</style></DisplayText><record><rec-number>147</rec-number><foreign-keys><keyapp="EN"db-id="fefzva2arafxvjeezt3vr2rhx22ervre0wt2"timestamp="1618075835">147</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Zhang,R.</author><author>Yan,F.</author><author>Chen,Y.</author></authors></contributors><auth-address>DepartmentofUltrasoundTheFirstAffiliatedHospitalofZhengzhouUniversityZhengzhouHenanProvince450052P.R.China. PaulC.LauterburResearchCenterforBiomedicalImagingInstituteofBiomedicalandHealthEngineeringShenzhenInstitutesofAdvancedTechnologyChineseAcademyofSciencesShenzhen518055P.R.China. StateKeyLaboratoryofHighPerformanceCeramicsandSuperfineMicrostructureShanghaiInstituteofCeramicsChineseAcademyofSciencesShanghai200050P.R.China.</auth-address><titles><title>ExogenousPhysicalIrradiationonTitaniaSemiconductors:MaterialsChemistryandTumor-SpecificNanomedicine</title><secondary-title>AdvSci(Weinh)</secondary-title></titles><periodical><full-title>AdvSci(Weinh)</full-title></periodical><pages>1801175</pages><volume>5</volume><number>12</number><edition>2018/12/26</edition><keywords><keyword>cancer</keyword><keyword>nanomedicine</keyword><keyword>physicalirradiation</keyword><keyword>semiconductors</keyword><keyword>titania</keyword></keywords><dates><year>2018</year><pub-dates><date>Dec</date></pub-dates></dates><isbn>2198-3844(Print) 2198-3844(Linking)</isbn><accession-num>30581710</accession-num><urls><related-urls><url>/pubmed/30581710</url></related-urls></urls><custom2>PMC6299725</custom2><electronic-resource-num>10.1002/advs.201801175</electronic-resource-num></record></Cite></EndNote>[\o"Zhang,2018#147"115]。Atsushi等人构建了核-壳结构的TiO2具有良好的SDT效果，产生的ROS在生理条件下有一定的细胞毒性ADDINEN.CITE<EndNote><Cite><Author>Harada</Author><Year>2013</Year><RecNum>148</RecNum><DisplayText><styleface="superscript">[116]</style></DisplayText><record><rec-number>148</rec-number><foreign-keys><keyapp="EN"db-id="fefzva2arafxvjeezt3vr2rhx22ervre0wt2"timestamp="1618076225">148</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Harada,A.</author><author>Ono,M.</author><author>Yuba,E.</author><author>Kono,K.</author></authors></contributors><auth-address>DepartmentofAppliedChemistry,GraduateSchoolofEngineering,OsakaPrefectureUniversity,1-1Gakuen-cho,Naka-ku,Sakai,Osaka599-8531,Japan.harada@chem.osakafu-u.ac.jp.</auth-address><titles><title>Titaniumdioxidenanoparticle-entrappedpolyioncomplexmicellesgeneratesingletoxygeninthecellsbyultrasoundirradiationforsonodynamictherapy</title><secondary-title>BiomaterSci</secondary-title></titles><periodical><full-title>BiomaterSci</full-title><abbr-1>Biomaterialsscience</abbr-1></periodical><pages>65-73</pages><volume>1</volume><number>1</number><edition>2013/01/30</edition><dates><year>2013</year><pub-dates><date>Jan30</date></pub-dates></dates><isbn>2047-4849(Electronic) 2047-4830(Linking)</isbn><accession-num>32481997</a