參考文獻(xiàn)參考文獻(xiàn)雜化細(xì)胞馬達(dá)的驅(qū)動方式及運(yùn)動控制研究國內(nèi)外文獻(xiàn)綜述目錄TOC\o"1-3"\h\u31376雜化細(xì)胞馬達(dá)的驅(qū)動方式及運(yùn)動控制研究國內(nèi)外文獻(xiàn)綜述 1241821.1趨化運(yùn)動 1185281.2磁場控制 3141401.3光控制 4雜化細(xì)胞馬達(dá)的運(yùn)動控制對雜化細(xì)胞馬達(dá)的設(shè)計和應(yīng)用至關(guān)重要，通過利用細(xì)胞或人工組分的特性，可以實(shí)現(xiàn)對雜化細(xì)胞馬達(dá)的運(yùn)動控制?？刂瓶梢允怯赏獠繄觯ɡ珉妶龌虼艌觯﹄s化馬達(dá)進(jìn)行控制，也可以由雜化馬達(dá)自身對環(huán)境因素（如溫度、趨化因子、pH等）產(chǎn)生響應(yīng)。例如雜化細(xì)菌馬達(dá)、雜化中性粒細(xì)胞馬達(dá)等，既可以對趨化因子梯度產(chǎn)生響應(yīng)，也可以根據(jù)外磁場方向進(jìn)行運(yùn)動。依賴細(xì)胞的自身的感知和響應(yīng)能力可以賦予細(xì)胞馬達(dá)自動導(dǎo)航的能力，但是細(xì)胞自身的感知和響應(yīng)過程例如化學(xué)趨化過程相對較慢，而外物理場可以實(shí)現(xiàn)對細(xì)胞雜化馬達(dá)的快速控制，但是需要實(shí)時成像和反饋回路，對于雜化細(xì)胞馬達(dá)的體內(nèi)應(yīng)用而言是一個挑戰(zhàn)。1.1趨化運(yùn)動雜化細(xì)胞馬達(dá)的趨化運(yùn)動及化學(xué)控制依賴于細(xì)胞自身的感知能力，細(xì)胞可以感知到其周圍化學(xué)分子的梯度，并能夠分辨其濃度。不同細(xì)胞能夠感受到的趨化因子、營養(yǎng)物質(zhì)、pH都能夠影響及控制能夠感知這些因素的雜化細(xì)胞馬達(dá)的運(yùn)動方向。趨化運(yùn)動及化學(xué)控制的一個顯著優(yōu)勢是，可以根據(jù)靶細(xì)胞的分子環(huán)境設(shè)計雜化細(xì)胞馬達(dá)，利用靶細(xì)胞釋放的化學(xué)分子誘導(dǎo)雜化細(xì)胞馬達(dá)運(yùn)動，因此雜化細(xì)胞馬達(dá)可以完成主動靶向。中性粒細(xì)胞對炎癥產(chǎn)生的細(xì)胞因子、細(xì)菌分泌物等能夠產(chǎn)生響應(yīng)，雜化中性粒細(xì)胞馬達(dá)能夠主動靶向炎癥部位、細(xì)菌等ADDINEN.CITE<EndNote><Cite><Author>Shao</Author><Year>2017</Year><RecNum>1179</RecNum><DisplayText><styleface="superscript">[12]</style></DisplayText><record><rec-number>1179</rec-number><foreign-keys><keyapp="EN"db-id="we95a2ppjztw2ler5pzv5vfkdetsataxd5fs"timestamp="0">1179</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Shao,Jingxin</author><author>Xuan,Mingjun</author><author>Zhang,Hongyue</author><author>Lin,Xiankun</author><author>Wu,Zhiguang</author><author>He,Qiang</author></authors></contributors><titles><title>Chemotaxis-GuidedHybridNeutrophilMicromotorsforTargetedDrugTransport</title><secondary-title>AngewandteChemieInternationalEdition</secondary-title></titles><periodical><full-title>AngewandteChemieInternationalEdition</full-title></periodical><pages>12935-12939</pages><volume>56</volume><number>42</number><keywords><keyword>biohybridmicromotors</keyword><keyword>chemotaxis</keyword><keyword>drugdelivery</keyword><keyword>mesoporoussilicananoparticles</keyword><keyword>neutrophils</keyword></keywords><dates><year>2017</year><pub-dates><date>2017/10/09</date></pub-dates></dates><publisher>JohnWiley&Sons,Ltd</publisher><isbn>1433-7851</isbn><urls><related-urls><url>/10.1002/anie.201706570</url></related-urls></urls><electronic-resource-num>10.1002/anie.201706570</electronic-resource-num><access-date>2020/06/15</access-date></record></Cite></EndNote>[12]。巨噬細(xì)胞能夠受到腫瘤細(xì)胞裂解液中的趨化因子刺激，產(chǎn)生定向遷移ADDINEN.CITE<EndNote><Cite><Author>Nguyen</Author><Year>2017</Year><RecNum>1326</RecNum><DisplayText><styleface="superscript">[80]</style></DisplayText><record><rec-number>1326</rec-number><foreign-keys><keyapp="EN"db-id="we95a2ppjztw2ler5pzv5vfkdetsataxd5fs"timestamp="1617348820">1326</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Nguyen,VanDu</author><author>Han,Jiwon</author><author>Go,Gwangjun</author><author>Zhen,Jin</author><author>Zheng,Shaohui</author><author>Le,VietHa</author><author>Park,Jong-Oh</author><author>Park,Sukho</author></authors></contributors><titles><title>Feasibilitystudyofdual-targetingpaclitaxel-loadedmagneticliposomesusingelectromagneticactuationandmacrophages</title><secondary-title>SensorsandActuatorsB:Chemical</secondary-title></titles><periodical><full-title>SensorsandActuatorsB:Chemical</full-title></periodical><pages>1226-1236</pages><volume>240</volume><keywords><keyword>Macrophage</keyword><keyword>Cell-mediateddrugdelivery</keyword><keyword>Liposome</keyword><keyword>Magneticnanoparticle</keyword><keyword>Tumortargeting</keyword></keywords><dates><year>2017</year><pub-dates><date>2017/03/01/</date></pub-dates></dates><isbn>0925-4005</isbn><urls><related-urls><url>/science/article/pii/S0925400516314940</url></related-urls></urls><electronic-resource-num>/10.1016/j.snb.2016.09.076</electronic-resource-num></record></Cite></EndNote>[80]。中性粒細(xì)胞和巨噬細(xì)胞可以用于通過趨化運(yùn)動靶向腫瘤部位。2013年，Park等人提出了一種基于細(xì)菌的微馬達(dá)，用于針對實(shí)體瘤的治療ADDINEN.CITE<EndNote><Cite><Author>Park</Author><Year>2013</Year><RecNum>1330</RecNum><DisplayText><styleface="superscript">[81]</style></DisplayText><record><rec-number>1330</rec-number><foreign-keys><keyapp="EN"db-id="we95a2ppjztw2ler5pzv5vfkdetsataxd5fs"timestamp="1617363923">1330</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Park,SungJun</author><author>Park,Seung-Hwan</author><author>Cho,Sunghoon</author><author>Kim,Deok-Mi</author><author>Lee,Yeonkyung</author><author>Ko,SeongYoung</author><author>Hong,Yeongjin</author><author>Choy,HyonE.</author><author>Min,Jung-Joon</author><author>Park,Jong-Oh</author><author>Park,Sukho</author></authors></contributors><titles><title>Newparadigmfortumortheranosticmethodologyusingbacteria-basedmicrorobot</title><secondary-title>ScientificReports</secondary-title></titles><periodical><full-title>ScientificReports</full-title></periodical><pages>3394</pages><volume>3</volume><dates><year>2013</year><pub-dates><date>Dec2</date></pub-dates></dates><isbn>2045-2322</isbn><accession-num>WOS:000327783800003</accession-num><urls><related-urls><url><styleface="underline"font="default"size="100%"><GotoISI>://WOS:000327783800003</style></url></related-urls></urls><custom7>3394</custom7><electronic-resource-num>10.1038/srep03394</electronic-resource-num></record></Cite></EndNote>[81]。該研究由鼠傷寒沙門氏菌（S.typhimurium）與cy5.5標(biāo)記的聚苯乙烯微球結(jié)合制備得到雜化細(xì)菌馬達(dá)（如圖1-12所示），雜化細(xì)菌馬達(dá)對實(shí)體瘤裂解物進(jìn)行趨化運(yùn)動，在活體實(shí)驗中，能夠在小鼠模型的腫瘤部位檢測到雜化細(xì)菌馬達(dá)的信號。雜化細(xì)菌馬達(dá)具有趨化運(yùn)動和腫瘤靶向能力。Zhuang等人使用多個粘性沙雷氏菌制備雜化細(xì)菌馬達(dá)，可以觀察到雜化細(xì)菌馬達(dá)對L-絲氨酸的趨化性運(yùn)動，在趨化性運(yùn)動時與無絲氨酸條件下運(yùn)動速度顯著上升，可能應(yīng)用在靶向藥物運(yùn)輸?shù)确矫鍭DDINEN.CITE<EndNote><Cite><Author>Zhuang</Author><Year>2016</Year><RecNum>1331</RecNum><DisplayText><styleface="superscript">[82]</style></DisplayText><record><rec-number>1331</rec-number><foreign-keys><keyapp="EN"db-id="we95a2ppjztw2ler5pzv5vfkdetsataxd5fs"timestamp="1617375842">1331</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Zhuang,Jiang</author><author>Sitti,Metin</author></authors></contributors><titles><title>Chemotaxisofbio-hybridmultiplebacteria-drivenmicroswimmers</title><secondary-title>ScientificReports</secondary-title></titles><periodical><full-title>ScientificReports</full-title></periodical><pages>32135</pages><volume>6</volume><dates><year>2016</year><pub-dates><date>Aug24</date></pub-dates></dates><isbn>2045-2322</isbn><accession-num>WOS:000381850600001</accession-num><urls><related-urls><url><styleface="underline"font="default"size="100%"><GotoISI>://WOS:000381850600001</style></url></related-urls></urls><custom7>32135</custom7><electronic-resource-num>10.1038/srep32135</electronic-resource-num></record></Cite></EndNote>[82]。圖1-12基于鼠傷寒沙門氏菌的雜化細(xì)菌馬達(dá)示意圖ADDINEN.CITE<EndNote><Cite><Author>Park</Author><Year>2013</Year><RecNum>1330</RecNum><DisplayText><styleface="superscript">[81]</style></DisplayText><record><rec-number>1330</rec-number><foreign-keys><keyapp="EN"db-id="we95a2ppjztw2ler5pzv5vfkdetsataxd5fs"timestamp="1617363923">1330</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Park,SungJun</author><author>Park,Seung-Hwan</author><author>Cho,Sunghoon</author><author>Kim,Deok-Mi</author><author>Lee,Yeonkyung</author><author>Ko,SeongYoung</author><author>Hong,Yeongjin</author><author>Choy,HyonE.</author><author>Min,Jung-Joon</author><author>Park,Jong-Oh</author><author>Park,Sukho</author></authors></contributors><titles><title>Newparadigmfortumortheranosticmethodologyusingbacteria-basedmicrorobot</title><secondary-title>ScientificReports</secondary-title></titles><periodical><full-title>ScientificReports</full-title></periodical><pages>3394</pages><volume>3</volume><dates><year>2013</year><pub-dates><date>Dec2</date></pub-dates></dates><isbn>2045-2322</isbn><accession-num>WOS:000327783800003</accession-num><urls><related-urls><url><styleface="underline"font="default"size="100%"><GotoISI>://WOS:000327783800003</style></url></related-urls></urls><custom7>3394</custom7><electronic-resource-num>10.1038/srep03394</electronic-resource-num></record></Cite></EndNote>[81]Fig.1-12SchemeofbiohybridbacteriamotorbasedonS.typhimuriumADDINEN.CITE<EndNote><Cite><Author>Park</Author><Year>2013</Year><RecNum>1330</RecNum><DisplayText><styleface="superscript">[81]</style></DisplayText><record><rec-number>1330</rec-number><foreign-keys><keyapp="EN"db-id="we95a2ppjztw2ler5pzv5vfkdetsataxd5fs"timestamp="1617363923">1330</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Park,SungJun</author><author>Park,Seung-Hwan</author><author>Cho,Sunghoon</author><author>Kim,Deok-Mi</author><author>Lee,Yeonkyung</author><author>Ko,SeongYoung</author><author>Hong,Yeongjin</author><author>Choy,HyonE.</author><author>Min,Jung-Joon</author><author>Park,Jong-Oh</author><author>Park,Sukho</author></authors></contributors><titles><title>Newparadigmfortumortheranosticmethodologyusingbacteria-basedmicrorobot</title><secondary-title>ScientificReports</secondary-title></titles><periodical><full-title>ScientificReports</full-title></periodical><pages>3394</pages><volume>3</volume><dates><year>2013</year><pub-dates><date>Dec2</date></pub-dates></dates><isbn>2045-2322</isbn><accession-num>WOS:000327783800003</accession-num><urls><related-urls><url><styleface="underline"font="default"size="100%"><GotoISI>://WOS:000327783800003</style></url></related-urls></urls><custom7>3394</custom7><electronic-resource-num>10.1038/srep03394</electronic-resource-num></record></Cite></EndNote>[81]人體內(nèi)許多細(xì)胞自身具有趨化能力，能夠響應(yīng)特定化學(xué)梯度，例如中性粒細(xì)胞等。Shao等2017年報道的雜化中性粒細(xì)胞馬達(dá)能夠感受大腸桿菌產(chǎn)生的趨化因子濃度梯度，并朝向大腸桿菌進(jìn)行運(yùn)動ADDINEN.CITE<EndNote><Cite><Author>Shao</Author><Year>2017</Year><RecNum>1179</RecNum><DisplayText><styleface="superscript">[12]</style></DisplayText><record><rec-number>1179</rec-number><foreign-keys><keyapp="EN"db-id="we95a2ppjztw2ler5pzv5vfkdetsataxd5fs"timestamp="0">1179</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Shao,Jingxin</author><author>Xuan,Mingjun</author><author>Zhang,Hongyue</author><author>Lin,Xiankun</author><author>Wu,Zhiguang</author><author>He,Qiang</author></authors></contributors><titles><title>Chemotaxis-GuidedHybridNeutrophilMicromotorsforTargetedDrugTransport</title><secondary-title>AngewandteChemieInternationalEdition</secondary-title></titles><periodical><full-title>AngewandteChemieInternationalEdition</full-title></periodical><pages>12935-12939</pages><volume>56</volume><number>42</number><keywords><keyword>biohybridmicromotors</keyword><keyword>chemotaxis</keyword><keyword>drugdelivery</keyword><keyword>mesoporoussilicananoparticles</keyword><keyword>neutrophils</keyword></keywords><dates><year>2017</year><pub-dates><date>2017/10/09</date></pub-dates></dates><publisher>JohnWiley&Sons,Ltd</publisher><isbn>1433-7851</isbn><urls><related-urls><url>/10.1002/anie.201706570</url></related-urls></urls><electronic-resource-num>10.1002/anie.201706570</electronic-resource-num><access-date>2020/06/15</access-date></record></Cite></EndNote>[12]。將大腸桿菌作為趨化源，可以引導(dǎo)雜化中性粒細(xì)胞馬達(dá)朝向趨化源進(jìn)行定向運(yùn)動，雜化中性粒細(xì)胞馬達(dá)的運(yùn)動速度、趨化指數(shù)、轉(zhuǎn)角分布、均方位移等受到趨化源處大腸桿菌濃度影響，說明趨化因子濃度梯度影響雜化細(xì)胞馬達(dá)的運(yùn)動行為。其中運(yùn)動速度、趨化指數(shù)、均方位移等均與大腸桿菌濃度呈正相關(guān)?；谮吇\(yùn)動的化學(xué)控制可以為雜化細(xì)胞馬達(dá)提供靈活的設(shè)計思路，并且化學(xué)控制基于細(xì)胞自身能力，不需要額外的功能化。但是不同細(xì)胞能夠感知的化學(xué)引誘劑和趨避劑種類繁多，因此高度的隨機(jī)性和較低的時間分辨率會影響趨化運(yùn)動對于雜化細(xì)胞馬達(dá)的控制。此外，化學(xué)梯度的形成及其強(qiáng)度受到化學(xué)物質(zhì)源頭的濃度和擴(kuò)散的限制，阻礙了遠(yuǎn)距離時雜化細(xì)胞馬達(dá)的趨化運(yùn)動。因此對于體內(nèi)應(yīng)用，理想條件下，趨化運(yùn)動應(yīng)當(dāng)與遠(yuǎn)程可控的控制方法（例如磁場等）結(jié)合使用?？梢酝ㄟ^遠(yuǎn)程控制將雜化細(xì)胞馬達(dá)首先引導(dǎo)至目標(biāo)部位附近，雜化細(xì)胞馬達(dá)利用趨化性完成進(jìn)一步的自主導(dǎo)航和驅(qū)動，從而精確靶向目標(biāo)部位。1.2磁場控制外磁場用于在雜化細(xì)胞馬達(dá)上產(chǎn)生磁扭矩，雜化細(xì)胞馬達(dá)磁矩與磁場方向?qū)R，導(dǎo)致雜化細(xì)胞馬達(dá)的驅(qū)動ADDINEN.CITEADDINEN.CITE.DATA[83,84]。使用磁場驅(qū)動及控制雜化細(xì)胞馬達(dá)的運(yùn)動，需要細(xì)胞自身或與其結(jié)合的人工組分具有磁性。一些細(xì)胞或微生物，例如MTB-1磁細(xì)菌ADDINEN.CITE<EndNote><Cite><Author>Taherkhani</Author><Year>2014</Year><RecNum>1325</RecNum><DisplayText><styleface="superscript">[85]</style></DisplayText><record><rec-number>1325</rec-number><foreign-keys><keyapp="EN"db-id="we95a2ppjztw2ler5pzv5vfkdetsataxd5fs"timestamp="1617328433">1325</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Taherkhani,Samira</author><author>Mohammadi,Mahmood</author><author>Daoud,Jamal</author><author>Martel,Sylvain</author><author>Tabrizian,Maryam</author></authors></contributors><titles><title>CovalentBindingofNanoliposomestotheSurfaceofMagnetotacticBacteriafortheSynthesisofSelf-PropelledTherapeuticAgents</title><secondary-title>ACSNano</secondary-title></titles><periodical><full-title>ACSNano</full-title></periodical><pages>5049-5060</pages><volume>8</volume><number>5</number><dates><year>2014</year><pub-dates><date>2014/05/27</date></pub-dates></dates><publisher>AmericanChemicalSociety</publisher><isbn>1936-0851</isbn><urls><related-urls><url>/10.1021/nn5011304</url></related-urls></urls><electronic-resource-num>10.1021/nn5011304</electronic-resource-num></record></Cite></EndNote>[85]，其內(nèi)部含有磁性晶體，自身具有磁性，使基于其的雜化細(xì)胞馬達(dá)能夠在磁場下進(jìn)行運(yùn)動。另一些天然細(xì)胞例如巨噬細(xì)胞ADDINEN.CITE<EndNote><Cite><Author>Han</Author><Year>2016</Year><RecNum>1322</RecNum><DisplayText><styleface="superscript">[38]</style></DisplayText><record><rec-number>1322</rec-number><foreign-keys><keyapp="EN"db-id="we95a2ppjztw2ler5pzv5vfkdetsataxd5fs"timestamp="1617241078">1322</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Han,Jiwon</author><author>Zhen,Jin</author><author>DuNguyen,Van</author><author>Go,Gwangjun</author><author>Choi,Youngjin</author><author>Ko,SeongYoung</author><author>Park,Jong-Oh</author><author>Park,Sukho</author></authors></contributors><titles><title>Hybrid-ActuatingMacrophage-BasedMicrorobotsforActiveCancerTherapy</title><secondary-title>ScientificReports</secondary-title></titles><periodical><full-title>ScientificReports</full-title></periodical><pages>28717</pages><volume>6</volume><number>1</number><dates><year>2016</year><pub-dates><date>2016/06/27</date></pub-dates></dates><isbn>2045-2322</isbn><urls><related-urls><url>/10.1038/srep28717</url></related-urls></urls><electronic-resource-num>10.1038/srep28717</electronic-resource-num></record></Cite></EndNote>[38]，中性粒細(xì)胞可以通過將磁性物質(zhì)吞噬、內(nèi)化，使自身具有磁性。除了以上兩種方式，還可以通過將磁性物質(zhì)添加至人工組分，將細(xì)胞與人工的磁性結(jié)構(gòu)結(jié)合，實(shí)現(xiàn)雜化細(xì)胞馬達(dá)的磁控運(yùn)動ADDINEN.CITEADDINEN.CITE.DATA[42,44]。磁場作為一種非侵入性，滲透力強(qiáng)，無傷害的驅(qū)動及控制方式，在生物相容性和安全性方面具有很大優(yōu)勢，同時可以對雜化細(xì)胞馬達(dá)實(shí)現(xiàn)精確控制，配合活體成像技術(shù)，磁場可以在活體內(nèi)驅(qū)動和控制雜化細(xì)胞馬達(dá)。Nguyen等人開發(fā)了一種由外磁場和巨噬細(xì)胞介導(dǎo)的雙重靶向藥物遞送系統(tǒng)ADDINEN.CITE<EndNote><Cite><Author>Nguyen</Author><Year>2017</Year><RecNum>1326</RecNum><DisplayText><styleface="superscript">[80]</style></DisplayText><record><rec-number>1326</rec-number><foreign-keys><keyapp="EN"db-id="we95a2ppjztw2ler5pzv5vfkdetsataxd5fs"timestamp="1617348820">1326</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Nguyen,VanDu</author><author>Han,Jiwon</author><author>Go,Gwangjun</author><author>Zhen,Jin</author><author>Zheng,Shaohui</author><author>Le,VietHa</author><author>Park,Jong-Oh</author><author>Park,Sukho</author></authors></contributors><titles><title>Feasibilitystudyofdual-targetingpaclitaxel-loadedmagneticliposomesusingelectromagneticactuationandmacrophages</title><secondary-title>SensorsandActuatorsB:Chemical</secondary-title></titles><periodical><full-title>SensorsandActuatorsB:Chemical</full-title></periodical><pages>1226-1236</pages><volume>240</volume><keywords><keyword>Macrophage</keyword><keyword>Cell-mediateddrugdelivery</keyword><keyword>Liposome</keyword><keyword>Magneticnanoparticle</keyword><keyword>Tumortargeting</keyword></keywords><dates><year>2017</year><pub-dates><date>2017/03/01/</date></pub-dates></dates><isbn>0925-4005</isbn><urls><related-urls><url>/science/article/pii/S0925400516314940</url></related-urls></urls><electronic-resource-num>/10.1016/j.snb.2016.09.076</electronic-resource-num></record></Cite></EndNote>[80]，如圖1-13，將包裹抗癌藥物（紫杉醇）的磁性脂質(zhì)體轉(zhuǎn)運(yùn)至腫瘤部位。利用巨噬細(xì)胞的吞噬能力將載藥磁性脂質(zhì)體內(nèi)化，制備得到雜化巨噬細(xì)胞馬達(dá)。利用磁場驅(qū)動和控制巨噬細(xì)胞，單個的巨噬細(xì)胞能夠沿程序規(guī)劃的路徑進(jìn)行運(yùn)動，速度可達(dá)10μm/s。同時利用趨化性，巨噬細(xì)胞馬達(dá)可以通過趨化運(yùn)動穿過多孔膜；將巨噬細(xì)胞馬達(dá)分別與乳腺癌細(xì)胞和結(jié)腸癌細(xì)胞共培養(yǎng)，驗證了巨噬細(xì)胞馬達(dá)對癌細(xì)胞的殺傷效果，并且通過使用巨噬細(xì)胞馬達(dá)運(yùn)載抗癌藥物，降低了殺死癌細(xì)胞所需的總給藥量。Yan等人報道了基于螺旋藻制備得到的雜化螺旋藻微馬達(dá)ADDINEN.CITE<EndNote><Cite><Author>Yan</Author><Year>2017</Year><RecNum>52</RecNum><DisplayText><styleface="superscript">[86]</style></DisplayText><record><rec-number>52</rec-number><foreign-keys><keyapp="EN"db-id="0v9arpfdqrxsp9esrsspdpw1f2sxvxz2552v"timestamp="1567985270">52</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Yan,Xiaohui</author><author>Zhou,Qi</author><author>Vincent,Melissa</author><author>Deng,Yan</author><author>Yu,Jiangfan</author><author>Xu,Jianbin</author><author>Xu,Tiantian</author><author>Tang,Tao</author><author>Bian,Liming</author><author>Wang,Yi-XiangJ.</author><author>Kostarelos,Kostas</author><author>Zhang,Li</author></authors></contributors><titles><title>Multifunctionalbiohybridmagnetitemicrorobotsforimaging-guidedtherapy</title><secondary-title>ScienceRobotics</secondary-title></titles><periodical><full-title>ScienceRobotics</full-title></periodical><pages>eaaq1155</pages><volume>2</volume><number>12</number><dates><year>2017</year></dates><urls><related-urls><url>/content/2/12/eaaq1155.abstract</url><url>/content/robotics/2/12/eaaq1155.full.pdf</url></related-urls></urls><electronic-resource-num>10.1126/scirobotics.aaq1155</electronic-resource-num></record></Cite></EndNote>[86]，通過磁場驅(qū)動和控制，雜化螺旋藻馬達(dá)能夠在各種生物流體中進(jìn)行可控運(yùn)動，在復(fù)雜的生物體內(nèi)流場中進(jìn)行高精度的導(dǎo)航，并能深入生物組織的內(nèi)部，以微創(chuàng)的方式診斷和治療疾病?；诼菪宓奶烊惶匦?，該馬達(dá)具有體內(nèi)熒光成像能力，并具有對癌細(xì)胞的毒性，能夠降解體外培養(yǎng)的癌細(xì)胞；通過在磁鐵礦微粒的懸浮液中進(jìn)行簡單的浸涂工藝處理，可以制備這種具有超順磁性的螺旋形狀的微馬達(dá)，并且由于磁性材料的吸附，這種雜化馬達(dá)可以通過磁共振成像技術(shù)進(jìn)行體內(nèi)追蹤。圖1-13磁場驅(qū)動內(nèi)部裝載載藥磁性脂質(zhì)體的雜化巨噬細(xì)胞馬達(dá)ADDINEN.CITE<EndNote><Cite><Author>Nguyen</Author><Year>2017</Year><RecNum>1326</RecNum><DisplayText><styleface="superscript">[80]</style></DisplayText><record><rec-number>1326</rec-number><foreign-keys><keyapp="EN"db-id="we95a2ppjztw2ler5pzv5vfkdetsataxd5fs"timestamp="1617348820">1326</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Nguyen,VanDu</author><author>Han,Jiwon</author><author>Go,Gwangjun</author><author>Zhen,Jin</author><author>Zheng,Shaohui</author><author>Le,VietHa</author><author>Park,Jong-Oh</author><author>Park,Sukho</author></authors></contributors><titles><title>Feasibilitystudyofdual-targetingpaclitaxel-loadedmagneticliposomesusingelectromagneticactuationandmacrophages</title><secondary-title>SensorsandActuatorsB:Chemical</secondary-title></titles><periodical><full-title>SensorsandActuatorsB:Chemical</full-title></periodical><pages>1226-1236</pages><volume>240</volume><keywords><keyword>Macrophage</keyword><keyword>Cell-mediateddrugdelivery</keyword><keyword>Liposome</keyword><keyword>Magneticnanoparticle</keyword><keyword>Tumortargeting</keyword></keywords><dates><year>2017</year><pub-dates><date>2017/03/01/</date></pub-dates></dates><isbn>0925-4005</isbn><urls><related-urls><url>/science/article/pii/S0925400516314940</url></related-urls></urls><electronic-resource-num>/10.1016/j.snb.2016.09.076</electronic-resource-num></record></Cite></EndNote>[80]a)巨噬細(xì)胞馬達(dá)制備示意圖；b)巨噬細(xì)胞馬達(dá)在磁場、趨化作用下靶向腫瘤部位過程示意圖；c)巨噬細(xì)胞馬達(dá)在磁場引導(dǎo)下運(yùn)動Fig.1-13Biohybridmacrophagemicromotorsloadedwithlipsomedrivenbymagneticfielda)Schemeofpreparationofmacrophagemicromotors;b)Macrophagemicromotorstargetingtotumorwithmagneticandchemotacticmotion;c)MagneticmotionofmacrophagemotorsYasa等人基于天然單細(xì)胞微生物衣藻構(gòu)建雜化馬達(dá)ADDINEN.CITE<EndNote><Cite><Author>Yasa</Author><Year>2018</Year><RecNum>1328</RecNum><DisplayText><styleface="superscript">[46]</style></DisplayText><record><rec-number>1328</rec-number><foreign-keys><keyapp="EN"db-id="we95a2ppjztw2ler5pzv5vfkdetsataxd5fs"timestamp="1617358398">1328</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Yasa,Oncay</author><author>Erkoc,Pelin</author><author>Alapan,Yunus</author><author>Sitti,Metin</author></authors></contributors><titles><title>Microalga-PoweredMicroswimmerstowardActiveCargoDelivery</title><secondary-title>AdvancedMaterials</secondary-title></titles><periodical><full-title>AdvancedMaterials</full-title></periodical><pages>1804130</pages><volume>30</volume><number>45</number><keywords><keyword>biohybrids</keyword><keyword>cargodelivery</keyword><keyword>Chlamydomonasreinhardtii</keyword><keyword>microalgae</keyword><keyword>microswimmers</keyword></keywords><dates><year>2018</year><pub-dates><date>2018/11/01</date></pub-dates></dates><publisher>JohnWiley&Sons,Ltd</publisher><isbn>0935-9648</isbn><work-type>/10.1002/adma.201804130</work-type><urls><related-urls><url>/10.1002/adma.201804130</url><url>/doi/full/10.1002/adma.201804130</url></related-urls></urls><electronic-resource-num>/10.1002/adma.201804130</electronic-resource-num><access-date>2021/04/02</access-date></record></Cite></EndNote>[46]，如圖1-10A，衣藻攜帶磁性聚電解質(zhì)膠囊，在磁場引導(dǎo)下進(jìn)行運(yùn)動。該衣藻馬達(dá)能夠在生理條件下進(jìn)行運(yùn)動，具有良好的生物相容性，可用于藥物的靶向遞送。Kim等人基于梨形四膜蟲構(gòu)建內(nèi)部含有Fe3O4磁性顆粒的雜化馬達(dá)ADDINEN.CITE<EndNote><Cite><Author>Kim</Author><Year>2010</Year><RecNum>1329</RecNum><DisplayText><styleface="superscript">[87]</style></DisplayText><record><rec-number>1329</rec-number><foreign-keys><keyapp="EN"db-id="we95a2ppjztw2ler5pzv5vfkdetsataxd5fs"timestamp="1617358470">1329</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Kim,DalHyung</author><author>Cheang,U.Kei</author><author>Kohidai,Laszlo</author><author>Byun,Doyoung</author><author>Kim,MinJun</author></authors></contributors><titles><title>ArtificialmagnetotacticmotioncontrolofTetrahymenapyriformisusingferromagneticnanoparticles:Atoolforfabricationofmicrobiorobots</title><secondary-title>AppliedPhysicsLetters</secondary-title></titles><periodical><full-title>AppliedPhysicsLetters</full-title></periodical><pages>173702</pages><volume>97</volume><number>17</number><dates><year>2010</year><pub-dates><date>Oct25</date></pub-dates></dates><isbn>0003-6951</isbn><accession-num>WOS:000284233600070</accession-num><urls><related-urls><url><styleface="underline"font="default"size="100%"><GotoISI>://WOS:000284233600070</style></url></related-urls></urls><custom7>173702</custom7><electronic-resource-num>10.1063/1.3497275</electronic-resource-num></record></Cite></EndNote>[87]，由電磁鐵控制雜化馬達(dá)的運(yùn)動，能夠完成可控的趨磁運(yùn)動。1.3光控制對于光敏的雜化細(xì)胞馬達(dá)，可以使用改變光源方向或控制光源開關(guān)的方式來控制雜化細(xì)胞馬達(dá)的運(yùn)動。光學(xué)控制可以提供對雜化細(xì)胞馬達(dá)的局部和特定波長的控制。Weibel等人基于單鞭毛、雙鞭毛的衣藻（Chlamydomonasreinhardtii）構(gòu)建雜化細(xì)胞馬達(dá)（如圖1-14所示）ADDINEN.CITEADDINEN.CITE.DATA[88]，利用表面化學(xué)修飾將聚苯乙烯微球附著在衣藻表面，通過趨光性引導(dǎo)雜化細(xì)胞馬達(dá)進(jìn)行運(yùn)動，雜化細(xì)胞馬達(dá)運(yùn)動速度可以達(dá)到100-200μm/s，運(yùn)動距離可達(dá)20cm。雜化衣藻馬達(dá)通過表面附著攜帶聚苯乙烯微球，不必在體外重新處理細(xì)胞，并且可以通過細(xì)胞提供動力，只需培養(yǎng)衣藻即可制備雜化衣藻馬達(dá)。衣藻運(yùn)動具有趨光運(yùn)動行為，并能完成聚苯乙烯微球的光化學(xué)釋放。圖1-14雜化衣藻馬達(dá)制備示意圖及透射電子顯微鏡照片F(xiàn)ig.1-14PreparationandTEMiamgeofbiohybridChlamydomonasmotors 鞭毛細(xì)菌可以在低雷諾數(shù)條件下進(jìn)行驅(qū)動，Steager等人使用群體運(yùn)動的粘性沙雷氏菌（Serratiamarcescens）驅(qū)動SU-8微結(jié)構(gòu)ADDINEN.CITE<EndNote><Cite><Author>Steager</Author><Year>2007</Year><RecNum>1337</RecNum><DisplayText><styleface="superscript">[89]</style></DisplayText><record><rec-number>1337</rec-number><foreign-keys><keyapp="EN"db-id="we95a2ppjztw2ler5pzv5vfkdetsataxd5fs"timestamp="1617673880">1337</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Steager,Edward</author><author>Kim,Chang-Beom</author><author>Patel,Jigarkumar</author><author>Bith,Socheth</author><author>Naik,Chandan</author><author>Reber,Lindsay</author><author>Kim,MinJun</author></authors></contributors><titles><title>Controlofmicrofabricatedstructurespoweredbyflagellatedbacteriausingphototaxis</title><secondary-title>AppliedPhysicsLetters</secondary-title></titles><periodical><full-title>AppliedPhysicsLetters</full-title></periodical><pages>263901</pages><volume>90</volume><number>26</number><dates><year>2007</year><pub-dates><date>Jun25</date></pub-dates></dates><isbn>0003-6951</isbn><accession-num>WOS:000247625500094</accession-num><urls><related-urls><url><styleface="underline"font="default"size="100%"><GotoISI>://WOS:000247625500094</style></url></related-urls></urls><custom7>263901</custom7><electronic-resource-num>10.1063/1.2752721</electronic-resource-num></record></Cite></EndNote>[89]。此研究中使用了局部照射紫外光控制鞭毛細(xì)菌的運(yùn)動，從而控制微結(jié)構(gòu)的運(yùn)動方向。此外，Vizsnyiczai等人研究了對基因工程處理后的大腸桿菌運(yùn)動速度的光控制ADDINEN.CITE<EndNote><Cite><Author>Vizsnyiczai</Author><Year>2017</Year><RecNum>1338</RecNum><DisplayText><styleface="superscript">[90]</style></DisplayText><record><rec-number>1338</rec-number><foreign-keys><keyapp="EN"db-id="we95a2ppjztw2ler5pzv5vfkdetsataxd5fs"timestamp="1617674746">1338</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Vizsnyiczai,Gaszton</author><author>Frangipane,Giacomo</author><author>Maggi,Claudio</author><author>Saglimbeni,Filippo</author><author>Bianchi,Silvio</author><author>DiLeonardo,Roberto</author></authors></contributors><titles><title>Lightcontrolled3Dmicromotorspoweredbybacteria</title><secondary-title>NatureCommunications</secondary-title></titles><periodical><full-title>NatureCommunications</full-title></periodical><pages>15974</pages><volume>8</volume><dates><year>2017</year><pub-dates><date>Jun28</date></pub-dates></dates><isbn>2041-1723</isbn><accession-num>WOS:000404226600001</accession-num><urls><related-urls><url><styleface="underline"font="default"size="100%"><GotoISI>://WOS:000404226600001</style></url></related-urls></urls><custom7>15974</custom7><electronic-resource-num>10.1038/ncomms15974</electronic-resource-num></record></Cite></EndNote>[90]，該細(xì)菌表達(dá)了一個光驅(qū)動的質(zhì)子泵，該泵可以通過隨光強(qiáng)改變調(diào)節(jié)大腸桿菌運(yùn)動速度。在光控運(yùn)動方面，由于可受光控制運(yùn)動的微生物的快速和特異性反應(yīng)，光控運(yùn)動是個較好的運(yùn)動方式。但是在雜化細(xì)胞馬達(dá)的體內(nèi)運(yùn)動及應(yīng)用方面，光控運(yùn)動受到光的滲透能力影響，較難在體內(nèi)應(yīng)用。體內(nèi)應(yīng)用同時應(yīng)考慮使用的光的波長，由于紫外光對生物組織的損傷，紫外光控制生物雜化馬達(dá)仍難以在體內(nèi)進(jìn)行應(yīng)用。參考文獻(xiàn)[1] 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Batchelor,T.,TemozolomideforMalignantBrainTumours[J].TheLancet,2000.355(9210):1115-1116.[9] 林顯坤,吳志光,司鐵巖,etal.,可控分子組裝的自驅(qū)動膠體馬達(dá)及其生物醫(yī)學(xué)應(yīng)用%J中國科學(xué):化學(xué)[J].2017.47(01):3-1