《腫瘤的聲動(dòng)力治療簡(jiǎn)介》3300字

腫瘤的聲動(dòng)力治療簡(jiǎn)介綜述1.1聲動(dòng)力治療的機(jī)制超聲波是一種頻率高于20000Hz的機(jī)械波，因?yàn)槠鋵?duì)人體作用的安全性，在臨床中常用于成像診斷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]。超聲的治療作用包括超聲吸收熱療與超聲熱消融手術(shù)等，它們都是基于超聲的熱效應(yīng)原理。聲動(dòng)力治療（Sonodynamictherapy，SDT）是以超聲波為主的新型治療手段，它可以用于動(dòng)脈粥樣硬化治療、抗細(xì)菌感染以及癌癥治療ADDINEN.CITEADDINEN.CITE.DATA[\o"Pang,2019#60"75-77]。1989年，SDT展現(xiàn)出雛形，相關(guān)報(bào)道發(fā)現(xiàn)了血卟啉在超聲存在下能導(dǎo)致更多的細(xì)胞損傷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發(fā)展而來(lái)，相比于PDT，超聲介導(dǎo)的SDT具有非侵害性、深組織穿透力、高精度等獨(dú)特的優(yōu)點(diǎn)，超聲能夠到達(dá)更深層次的器官，如胰腺、肝臟和腫瘤。研究人員為了闡明SDT的機(jī)制，最初是將PDT的機(jī)制順推到到SDT當(dāng)中。然而實(shí)際上SDT作用的原理更加復(fù)雜，不像PDT引起光動(dòng)力效應(yīng)是單一的由光輻射激活光敏劑通過(guò)能量及電子轉(zhuǎn)移等過(guò)程誘導(dǎo)產(chǎn)生活性氧（Reactiveoxygenspecies，ROS）ADDINEN.CITEADDINEN.CITE.DATA[\o"Li,2020#106"79,\o"Im,2021#107"80]。SDT由于其復(fù)雜的過(guò)程，現(xiàn)今仍未明確其作用的機(jī)制。但經(jīng)過(guò)科研人員的不斷努力，已經(jīng)發(fā)現(xiàn)了SDT的部分機(jī)制（圖1-5），其中包括了ROS的產(chǎn)生、空化氣穴效應(yīng)、熱效應(yīng)及直接誘導(dǎo)細(xì)胞凋亡等ADDINEN.CITEADDINEN.CITE.DATA[\o"Hiraoka,2006#67"81-83]。首先，SDT與PDT有較為類似的一點(diǎn)，都能夠通過(guò)激活其各自的敏化劑產(chǎn)生ROS，并誘導(dǎo)細(xì)胞死亡。在SDT中，超聲波的能量激活了聲敏劑，通過(guò)類似PDT的原理產(chǎn)生了ROS，這是大多數(shù)文章都報(bào)道過(guò)的一種機(jī)制，也是最廣為接受的機(jī)制。超聲介導(dǎo)的ROS能夠增強(qiáng)細(xì)胞膜的通透性和刺激Ca2+通過(guò)離子通道內(nèi)流ADDINEN.CITEADDINEN.CITE.DATA[\o"Zhang,2014#116"84,\o"Zhang,2018#117"85]。其次，超聲波輻射時(shí)，部分能量傳輸?shù)街車橘|(zhì)中，將會(huì)引起對(duì)流運(yùn)動(dòng)，稱作“聲流”。氣態(tài)內(nèi)含物如微泡在超聲振蕩下，部分區(qū)域會(huì)發(fā)生這種對(duì)流運(yùn)動(dòng)并存在剪切應(yīng)力，在這種情況下，會(huì)產(chǎn)生“非慣性”的空腔。隨著持續(xù)的超聲振蕩，這些空腔會(huì)急速內(nèi)縮并發(fā)生內(nèi)爆，在極短暫的時(shí)間內(nèi)產(chǎn)生極高的熱量，這一氣穴形成、振蕩并塌縮的周期過(guò)程是超聲處理下非常重要的一個(gè)機(jī)械效應(yīng)。在對(duì)細(xì)胞超聲時(shí)，這種機(jī)械效應(yīng)能引起瞬態(tài)膜孔隙、細(xì)胞膜變形等結(jié)果ADDINEN.CITEADDINEN.CITE.DATA[\o"Hassan,2010#120"86,\o"vanWamel,2006#121"87]。這種機(jī)械效應(yīng)被很多報(bào)道稱為“空化效應(yīng)”。很多實(shí)驗(yàn)證明，超聲波能夠在細(xì)胞或組織液中產(chǎn)生極小的氣泡空穴，氣泡在超聲的作用下振動(dòng)，隨之發(fā)生急速膨脹并塌縮，這個(gè)過(guò)程使空穴內(nèi)溫度在極短的時(shí)間內(nèi)超過(guò)了5000K?？栈饔卯a(chǎn)生的局部高溫高壓會(huì)誘導(dǎo)區(qū)域內(nèi)發(fā)生一系列自由基反應(yīng)，包括空穴內(nèi)部、空穴與溶劑相交的界面，最終呈現(xiàn)出超聲化學(xué)效應(yīng)，而且空化效應(yīng)是多元控制的，超聲波的頻率與強(qiáng)度、環(huán)境的溫度與壓力、溶液的粘度等參數(shù)的變化都會(huì)影響著空化效應(yīng)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等人的實(shí)驗(yàn)結(jié)果顯示低頻率超聲可能導(dǎo)致更強(qiáng)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]。超聲的熱效應(yīng)會(huì)隨著聲波的占空比而改變，脈沖波產(chǎn)生的熱效應(yīng)會(huì)小于連續(xù)超聲波，且脈沖波也足以產(chǎn)生空化活性，因此調(diào)整脈沖波的使用可以用于調(diào)節(jié)超聲產(chǎn)生的熱效應(yīng)與空化效用。此外，超聲空化對(duì)生物組織還有一種獨(dú)特的效應(yīng)，稱為聲孔效應(yīng)（Sonoporation）。在生物組織液中存在許多微小氣泡，超聲波激活這些氣泡產(chǎn)生了空化作用。當(dāng)空化氣穴塌縮，其蘊(yùn)含的能量有的被均勻地釋放到周圍環(huán)境中，而另一些不對(duì)稱的氣穴塌縮時(shí)會(huì)從一個(gè)角度噴射高速液體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]。不論是哪一種，隨著空穴的形成與潰滅，局域內(nèi)爆發(fā)的能量影響著周圍的環(huán)境，細(xì)胞膜表面的空化過(guò)程會(huì)導(dǎo)致膜產(chǎn)生孔狀結(jié)構(gòu)，使細(xì)胞膜通透性增加，一些難以透過(guò)活細(xì)胞膜的藥物分子此時(shí)可以通過(guò)內(nèi)吞進(jìn)入細(xì)胞ADDINEN.CITEADDINEN.CITE.DATA[\o"Yu,2014#71"91-94]。這種聲孔效應(yīng)在低功率的超聲條件下發(fā)生是瞬時(shí)的、可恢復(fù)的，并且它對(duì)細(xì)胞膜作用產(chǎn)生的孔徑能夠達(dá)到150nm，現(xiàn)在它已被用做提高藥物遞送的一種方式，比如提高基因轉(zhuǎn)染率ADDINEN.CITEADDINEN.CITE.DATA[\o"Castle,2016#73"95-97]。聲孔效應(yīng)常與超聲造影劑微泡聯(lián)合作用，以達(dá)到更好的藥物靶向輸送效率。因?yàn)槌晫?duì)氣體的反射比對(duì)液體大得多（近1000倍），超聲造影劑由于其含有的氣泡可以增強(qiáng)超聲的散射回聲，可以提高超聲影像的分辨率。氣泡在SDT中可能扮演著一個(gè)重要的角色，有著提高SDT效果的潛在效用。除了機(jī)械效應(yīng)之外，熱效應(yīng)是超聲治療最早利用的一種機(jī)制。高強(qiáng)度聚焦超聲（Highintensityfocusedultrasound，HIFU）已被用于熱效應(yīng)治療（癌癥熱消融治療），它能夠在幾秒內(nèi)將局部溫度升至70℃以上，對(duì)組織造成不可逆轉(zhuǎn)的損傷ADDINEN.CITEADDINEN.CITE.DATA[\o"Maeshige,2020#112"98]。超聲的熱效應(yīng)是多種因素共同決定的結(jié)果，超聲頻率、聚焦程度、持續(xù)脈沖時(shí)間、超聲輻射時(shí)間和吸收系數(shù)在超聲引起溫度升高的過(guò)程中起著決定作用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，對(duì)人體進(jìn)行超聲，超聲波束在傳播路徑上遇到液體，溫度只有微弱的上升；相反，當(dāng)在高度吸收的組織（如骨骼）中發(fā)傳播，則溫度會(huì)有較之明顯的上升。同時(shí)聚焦程度也極大影響著超聲熱效應(yīng)，HIFU便是利用了這一點(diǎn)，提高熱效應(yīng)的同時(shí)縮小了治療范圍，精準(zhǔn)熱消融病變區(qū)域。聚焦超聲波還是非侵入性、針對(duì)性打開(kāi)血腦屏障（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]。圖1-5SDT的機(jī)制圖示。1O2：?jiǎn)尉€態(tài)氧；OH：羥基自由基；HO2·：超氧自由基ADDINEN.CITEADDINEN.CITE.DATA[\o"Pan,2018#298"101]。超聲的熱效應(yīng)也有某種獨(dú)特的生理作用。超聲波從探頭發(fā)射，傳播路徑的分子在壓縮和膨脹的周期中振動(dòng)，能量依靠這個(gè)過(guò)程從探頭處傳播到了目標(biāo)位置，這種能量傳輸便引起了一定程度的升溫。超聲波引發(fā)的體溫升高能提高細(xì)胞中的藥物攝取，對(duì)抗耐藥性ADDINEN.CITEADDINEN.CITE.DATA[\o"Liu,2001#119"102]。超聲與細(xì)胞相互作用并加強(qiáng)細(xì)胞對(duì)小分子藥物的攝取受多種因素制約，包括超聲參數(shù)，細(xì)胞屬性等。其中細(xì)胞的結(jié)構(gòu)、大小和彈性因細(xì)胞株不同而各異，且即使同一株細(xì)胞，其細(xì)胞特性也會(huì)因細(xì)胞密度、細(xì)胞周期相而變化。超聲對(duì)不同類型的細(xì)胞誘導(dǎo)膜滲透的作用時(shí)間有顯著差異ADDINEN.CITEADDINEN.CITE.DATA[\o"Lammertink,2015#118"103]。SDT主要側(cè)重于非熱效應(yīng)，利用低強(qiáng)度的超聲通過(guò)多種機(jī)制激活聲敏劑并引起細(xì)胞損傷，最終導(dǎo)致細(xì)胞壞死或凋亡。一些研究表明超聲波還會(huì)引起線粒體膜電位的變化、細(xì)胞膜損傷及DNA裂解等特征，證明了超聲波能夠誘發(fā)細(xì)胞凋亡ADDINEN.CITEADDINEN.CITE.DATA[\o"Feril,2002#109"104-106]。Noriaki等人的研究顯示超聲波在細(xì)胞膜上造成小孔引起細(xì)胞凋亡ADDINEN.CITEADDINEN.CITE.DATA[\o"Maeshige,2020#112"98]。超聲除了可用于SDT和HIFU等治療手段，它還會(huì)對(duì)納米粒產(chǎn)生一些物理化學(xué)的改變，比如改變納米流體的粘度和穩(wěn)定性，減少團(tuán)簇的大小，提高膠體的分散性和穩(wěn)定性等ADDINEN.CITEADDINEN.CITE.DATA[\o"Asadi,2019#115"107]?？傮w來(lái)說(shuō)，關(guān)于SDT的機(jī)制可能不是共通的，會(huì)受到聲敏劑，超聲參數(shù)和生物模型的性質(zhì)等多種要素影響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聲敏劑SDT要達(dá)到良好的效果需要三個(gè)元素：低強(qiáng)度超聲，聲敏劑以及氧分子，聲敏劑是其中的關(guān)鍵元素ADDINEN.CITEADDINEN.CITE.DATA[\o"Pang,2016#108"108]。產(chǎn)生ROS是SDT重要的機(jī)制之一，它與靶向化療藥結(jié)合具有優(yōu)秀的協(xié)同療效。聲敏劑（Sonosensitizers）是在超聲作用下能夠產(chǎn)生ROS的化合物，是超聲與氧分子之間的橋梁。類似于光敏劑（Photosensitizers），聲敏劑在一定頻率強(qiáng)度的超聲輻射下，分子從基態(tài)被激活到激發(fā)態(tài)再返回基態(tài)的過(guò)程中，聲敏劑釋放能量轉(zhuǎn)移到附近的氧分子，進(jìn)而產(chǎn)生ROS。聲敏劑不在超聲作用時(shí)呈現(xiàn)低毒性。在過(guò)去的幾十年里已經(jīng)研究和開(kāi)發(fā)了多種類型的聲敏劑，包括有機(jī)分子、無(wú)機(jī)納米材料和基于金屬的材料。第一代被開(kāi)發(fā)使用的聲敏劑是卟啉類。其中常見(jiàn)的有原卟啉IX（PPIX）、血卟啉（Hp）、血卟啉單甲基醚（HMME）以及其他卟啉衍生物。赤蘚紅B（EB）和玫瑰紅（RB）作為氧雜蒽類聲敏劑，也表現(xiàn)出不俗的聲動(dòng)效率。其中RB的各種衍生物還展現(xiàn)出了光聲動(dòng)力協(xié)同作用，在肝癌細(xì)胞中表現(xiàn)出顯著的抗癌效果ADDINEN.CITEADDINEN.CITE.DATA[\o"Chen,2018#277"109]。二氫卟吩e6（Ce6）是一種天然，一些研究證明Ce6也具有聲動(dòng)力抗腫瘤效果，超聲提高細(xì)胞對(duì)納米藥物的攝取從而增強(qiáng)了SDT的效果ADDINEN.CITEADDINEN.CITE.DATA[\o"Wang,2018#271"110,\o"Li,2014#273"111]。Ce6和親水性聚乙烯吡咯烷酮（PVP）結(jié)合形成了光子（Photolon）ADDINEN.CITEADDINEN.CITE.DATA[\o"Copley,2008#275"112]，這是一種極有前景的光敏劑，已經(jīng)被批準(zhǔn)用于臨床。吲哚菁綠（ICG）是一種小分子聲敏劑，以被FDA批準(zhǔn)用于光學(xué)醫(yī)學(xué)成像和診斷ADDINEN.CITEADDINEN.CITE.DATA[\o"Newton,2019#281"113]，有研究報(bào)道包裹ICG的功能脂質(zhì)微粒在卵巢癌中實(shí)現(xiàn)了靶向光聲成像且表現(xiàn)出不俗的光聲動(dòng)力與光熱協(xié)同抗腫瘤效應(yīng)ADDINEN.CITEADDINEN.CITE.DATA[\o"Liu,2019#279"114]。無(wú)機(jī)納米材料也被用作聲敏劑，與有機(jī)小分子相比，它們具有更為優(yōu)越的物理化學(xué)特性和穩(wěn)定性。二氧化鈦（TiO2）是一種典型的半導(dǎo)體，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等人構(gòu)建了核-殼結(jié)構(gòu)的TiO2具有良好的SDT效果，產(chǎn)生的ROS在生理?xiàng)l件下有一定的細(xì)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