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参考文献参考文献杂化细胞马达在生物医学领域的应用研究国内外文献综述目录TOC\o"1-3"\h\u25899杂化细胞马达在生物医学领域的应用研究国内外文献综 1300041.1成像诊断 1311931.2辅助生殖 1219111.3靶向药物递送 21.1成像诊断实时跟踪和定位杂化细胞马达对于反馈和外部控制至关重要,目前的超声、红外、MRI等成像技术仍然难以针对单个杂化细胞马达进行成像ADDINEN.CITE<EndNote><Cite><Author>Medina-Sanchez</Author><Year>2017</Year><RecNum>1348</RecNum><DisplayText><styleface="superscript">[91]</style></DisplayText><record><rec-number>1348</rec-number><foreign-keys><keyapp="EN"db-id="we95a2ppjztw2ler5pzv5vfkdetsataxd5fs"timestamp="1618016339">1348</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Medina-Sanchez,Mariana</author><author>Schmidt,OliverG.</author></authors></contributors><titles><title>Medicalmicrobotsneedbetterimagingandcontrol</title><secondary-title>Nature</secondary-title></titles><periodical><full-title>Nature</full-title></periodical><pages>406-408</pages><volume>545</volume><number>7655</number><dates><year>2017</year><pub-dates><date>May25</date></pub-dates></dates><isbn>0028-0836</isbn><accession-num>WOS:000401906500025</accession-num><urls><related-urls><url><GotoISI>://WOS:000401906500025</url></related-urls></urls><electronic-resource-num>10.1038/545406a</electronic-resource-num></record></Cite><Cite><Author>Medina-Sanchez</Author><Year>2017</Year><RecNum>1348</RecNum><record><rec-number>1348</rec-number><foreign-keys><keyapp="EN"db-id="we95a2ppjztw2ler5pzv5vfkdetsataxd5fs"timestamp="1618016339">1348</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Medina-Sanchez,Mariana</author><author>Schmidt,OliverG.</author></authors></contributors><titles><title>Medicalmicrobotsneedbetterimagingandcontrol</title><secondary-title>Nature</secondary-title></titles><periodical><full-title>Nature</full-title></periodical><pages>406-408</pages><volume>545</volume><number>7655</number><dates><year>2017</year><pub-dates><date>May25</date></pub-dates></dates><isbn>0028-0836</isbn><accession-num>WOS:000401906500025</accession-num><urls><related-urls><url><GotoISI>://WOS:000401906500025</url></related-urls></urls><electronic-resource-num>10.1038/545406a</electronic-resource-num></record></Cite></EndNote>[91]。在最近的发展中,通过不同的成像技术(例如MRI和荧光成像),群体的杂化细胞马达已经可以在医学成像和诊断等功能中起到作用。Yan等报道了一种基于螺旋藻制备的螺旋藻杂化磁性马达,具备超顺磁性,能在生物流体中进行运动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]。基于天然螺旋藻的荧光特性,杂化螺旋藻马达能够用于荧光成像、远程诊断等。基于Fe3O4的修饰层提供了MRI成像能力,通过磁共振成像可以追踪体内的杂化马达群体运动。MRI成像在渗透力方面相对与荧光成像具有显著优势,荧光的渗透能力有限,难以对体内器官进行成像。 Vilela等人使用正电子发射断层扫描(PET),用于对Au/PEDOT/Pt管状微马达的成像ADDINEN.CITE<EndNote><Cite><Author>Vilela</Author><Year>2018</Year><RecNum>1349</RecNum><DisplayText><styleface="superscript">[92]</style></DisplayText><record><rec-number>1349</rec-number><foreign-keys><keyapp="EN"db-id="we95a2ppjztw2ler5pzv5vfkdetsataxd5fs"timestamp="1618022193">1349</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Vilela,Diana</author><author>Cossío,Unai</author><author>Parmar,Jemish</author><author>Martínez-Villacorta,AngelM.</author><author>Gómez-Vallejo,Vanessa</author><author>Llop,Jordi</author><author>Sánchez,Samuel</author></authors></contributors><titles><title>MedicalImagingfortheTrackingofMicromotors</title><secondary-title>ACSNano</secondary-title></titles><periodical><full-title>ACSNano</full-title></periodical><pages>1220-1227</pages><volume>12</volume><number>2</number><dates><year>2018</year><pub-dates><date>2018/02/27</date></pub-dates></dates><publisher>AmericanChemicalSociety</publisher><isbn>1936-0851</isbn><urls><related-urls><url>/10.1021/acsnano.7b07220</url></related-urls></urls><electronic-resource-num>10.1021/acsnano.7b07220</electronic-resource-num></record></Cite></EndNote>[92]。通过马达表面吸附碘同位素提供PET成像性能,为杂化细胞马达的体内成像提供了新方式。1.2辅助生殖无法正确定向和游动的精子细胞引起了生育缺陷,导致不育。杂化精子马达可以通过将精子细胞与人工组分结合,通过人工组分帮助精子进行运动,在不影响其健康的前提下实现其目标,从而实现辅助受精和进一步的辅助生殖。远程非侵入性的运动控制方式(例如磁场)帮助杂化精子马达靶向其目标部位,完成辅助生殖任务。辅助生殖是杂化细胞马达的又一个重要的应用方向,尤其是对杂化精子马达来说。杂化精子马达的增强运动性能正适合于推动精子细胞到达卵细胞附近,以完成受精作用。临床数据指出,即使是最先进的辅助生殖技术,其成功率依然较低,这些技术包括从体内取出卵子、在体外的培养皿中受精、胚胎培养以及将胚胎重新植入子宫;这些步骤需要依靠在显微镜下的高精度操作,并且对备孕的母体有较高的要求。在这里,杂化细胞马达可以帮助绕过这些冗长的、充满高风险与高成本的步骤,并通过引导将杂化精子马达引导至人体内的目标卵细胞中。例如,O.Schmidt等人利用带有铁成分的50μm长微管包封牛的精子,精子细胞的鞭毛用于推动微管向前运动,而含铁的微管可以通过远程无线的磁场操控其方向ADDINEN.CITE<EndNote><Cite><Author>Magdanz</Author><Year>2014</Year><RecNum>1392</RecNum><DisplayText><styleface="superscript">[93]</style></DisplayText><record><rec-number>1392</rec-number><foreign-keys><keyapp="EN"db-id="we95a2ppjztw2ler5pzv5vfkdetsataxd5fs"timestamp="1618058291">1392</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Magdanz,Veronika</author><author>Schmidt,OliverG.</author></authors></contributors><titles><title>Spermbots:potentialimpactfordrugdeliveryandassistedreproductivetechnologies</title><secondary-title>ExpertOpiniononDrugDelivery</secondary-title></titles><periodical><full-title>ExpertOpiniononDrugDelivery</full-title></periodical><pages>1125-1129</pages><volume>11</volume><number>8</number><dates><year>2014</year><pub-dates><date>Aug</date></pub-dates></dates><isbn>1742-5247</isbn><accession-num>WOS:000340258600001</accession-num><urls><related-urls><url><GotoISI>://WOS:000340258600001</url></related-urls></urls><electronic-resource-num>10.1517/17425247.2014.924502</electronic-resource-num></record></Cite></EndNote>[93]。此外,具有来自光学显微镜反馈的电磁线圈可用于对杂化精子马达进行闭环控制,以将其定向输送到选定的参考点。Schmidt等人还研究了微管半径、微管内精子细胞的穿透程度以及温度对杂化精子马达速度的影响ADDINEN.CITE<EndNote><Cite><Author>Magdanz</Author><Year>2015</Year><RecNum>1402</RecNum><DisplayText><styleface="superscript">[94]</style></DisplayText><record><rec-number>1402</rec-number><foreign-keys><keyapp="EN"db-id="we95a2ppjztw2ler5pzv5vfkdetsataxd5fs"timestamp="1618060397">1402</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Magdanz,Veronika</author><author>Medina-Sanchez,Mariana</author><author>Chen,Yan</author><author>Guix,Maria</author><author>Schmidt,OliverG.</author></authors></contributors><titles><title>HowtoImproveSpermbotPerformance</title><secondary-title>AdvancedFunctionalMaterials</secondary-title></titles><periodical><full-title>AdvancedFunctionalMaterials</full-title></periodical><pages>2763-2770</pages><volume>25</volume><number>18</number><dates><year>2015</year><pub-dates><date>May13</date></pub-dates></dates><isbn>1616-301X</isbn><accession-num>WOS:000354365600015</accession-num><urls><related-urls><url><GotoISI>://WOS:000354365600015</url></related-urls></urls><electronic-resource-num>10.1002/adfm.201500015</electronic-resource-num></record></Cite></EndNote>[94]。已经发现的是,精子穿透微管的程度会随微管半径的增加而增加;由于鞭毛的封闭性增加,具有较高渗透率的精子的速度会降低;还观察到速度随温度的增加而增加。一般而言,杂化精子马达的速度较单独的精子大大下降,一般只有初始精子速度的10%左右,在这种情况下,精子与微管间的作用倾向于随即发生,导致二者间耦合效率较低。为了提高杂化精子马达的运动性能,该研究团队将微管的长度从50μm缩短到20μm,使杂化精子马达的运动速度从每秒约20%体长增加到每秒约65%体长。为了进一步提高杂化精子马达的辅助生殖能力,提出了使用纤连蛋白将精子细胞结合到微管的中空空间,并向环境中添加咖啡因以增强细胞的运动性。如上所述,有几种生物分子可用于将精子细胞结合到微管的内表面ADDINEN.CITEADDINEN.CITE.DATA[95-97]。由于微管是掺杂铁磁性材料的,因此可以使用外部磁场来控制和维持其方向。因此,尽管未耦合的精子细胞的推进是随机的,但是可以使用永磁体或电磁体产生的外部磁场来高度控制已耦合的杂化精子马达的推进方向。1.3靶向药物递送人工组分与细胞结合形成杂化细胞马达,人工组分是杂化马达的关键组成部分。可通过装载在人工组分表面或内部空间的分子和颗粒为杂化马达提供新功能,例如磁驱动和药物递送等ADDINEN.CITE<EndNote><Cite><Author>Leonardo</Author><Year>2015</Year><RecNum>1370</RecNum><DisplayText><styleface="superscript">[98]</style></DisplayText><record><rec-number>1370</rec-number><foreign-keys><keyapp="EN"db-id="we95a2ppjztw2ler5pzv5vfkdetsataxd5fs"timestamp="1618044211">1370</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Leonardo,Ricotti</author><author>Andrea,Cafarelli</author><author>Veronica,Iacovacci</author><author>Lorenzo,Vannozzi</author><author>Arianna,Menciassi</author></authors></contributors><titles><title>AdvancedMicro-Nano-BioSystemsforFutureTargetedTherapies</title><secondary-title>CurrentNanoscience</secondary-title></titles><periodical><full-title>CurrentNanoscience</full-title></periodical><pages>144-160</pages><volume>11</volume><number>2</number><keywords><keyword>Drugdelivery</keyword><keyword>micro-nano-biosystems</keyword><keyword>microrobotics</keyword><keyword>nanocarriers</keyword><keyword>nanomedicine</keyword><keyword>nanorobotics</keyword><keyword>nanotechnology</keyword><keyword>targetedtherapy.</keyword></keywords><dates><year>2015</year></dates><isbn>1573-4137/1875-6786</isbn><urls><related-urls><url>/node/126122/article</url></related-urls></urls><electronic-resource-num>/10.2174/1573413710666141114221246</electronic-resource-num></record></Cite></EndNote>[98]。杂化细胞马达的载药能力取决于构成人工组分的材料,使用多孔材料(例如水凝胶)或囊泡(脂质体、细胞膜等)可以实现有效的药物装载。杂化细胞马达可以装载紫杉醇ADDINEN.CITE<EndNote><Cite><Author>Nguyen</Author><Year>2016</Year><RecNum>1321</RecNum><DisplayText><styleface="superscript">[99]</style></DisplayText><record><rec-number>1321</rec-number><foreign-keys><keyapp="EN"db-id="we95a2ppjztw2ler5pzv5vfkdetsataxd5fs"timestamp="1617199338">1321</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Nguyen,VanDu</author><author>Han,Ji-Won</author><author>Choi,YoungJin</author><author>Cho,Sunghoon</author><author>Zheng,Shaohui</author><author>Ko,SeongYoung</author><author>Park,Jong-Oh</author><author>Park,Sukho</author></authors></contributors><titles><title>Activetumor-therapeuticliposomalbacteriobotcombiningadrug(paclitaxel)-encapsulatedliposomewithtargetingbacteria(SalmonellaTyphimurium)</title><secondary-title>SensorsandActuatorsB:Chemical</secondary-title></titles><periodical><full-title>SensorsandActuatorsB:Chemical</full-title></periodical><pages>217-224</pages><volume>224</volume><keywords><keyword>Liposome</keyword><keyword>Microrobot</keyword><keyword>Paclitaxel</keyword><keyword>Tumortherapy</keyword><keyword>Bacterialactuation</keyword></keywords><dates><year>2016</year><pub-dates><date>2016/03/01/</date></pub-dates></dates><isbn>0925-4005</isbn><urls><related-urls><url>/science/article/pii/S0925400515303415</url></related-urls></urls><electronic-resource-num>/10.1016/j.snb.2015.09.034</electronic-resource-num></record></Cite></EndNote>[99]、阿霉素、mRNA、环丙沙星等药物分子,载体包括纳米脂质体、聚乳酸-乙醇酸(PLGA)颗粒,介孔二氧化硅和聚电解质多层等,证明了载药杂化细胞马达的成功运行。纳米颗粒或药物分子还可装载在细胞膜或细胞质之内,并且可以通过刺激响应释放,因此可以针对病变部位进行靶向药物递送。一些细菌具有和肿瘤组织通讯的能力ADDINEN.CITEADDINEN.CITE.DATA[81,100],Yu等2004年报道了静脉注射到活体动物中的细菌进入实体瘤和转移瘤中,并可进行繁殖。鼠伤寒沙门氏菌等可以进行荧光素酶催化的发光或表达绿色荧光蛋白,通过细菌在体内繁殖的动物实验活体成像结果,证明了鼠伤寒沙门氏菌的肿瘤靶向能力,以及在肿瘤中存活和复制的能力。Choy等人报道了改造后表达细菌荧光素酶的大肠杆菌,将大肠杆菌注射至小鼠体内,大肠杆菌具有肿瘤靶向能力,能够实时检测肿瘤中细菌迁移,同时具有非侵入性成像能力。显示了杂化细菌马达具有转移瘤检测和肿瘤特异性基因治疗的潜力ADDINEN.CITE<EndNote><Cite><Author>Min</Author><Year>2008</Year><RecNum>1351</RecNum><DisplayText><styleface="superscript">[101]</style></DisplayText><record><rec-number>1351</rec-number><foreign-keys><keyapp="EN"db-id="we95a2ppjztw2ler5pzv5vfkdetsataxd5fs"timestamp="1618035945">1351</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Min,Jung-Joon</author><author>Kim,Hyun-Ju</author><author>Park,JaeHyo</author><author>Moon,Sungmin</author><author>Jeong,JaeHo</author><author>Hong,Yeoung-Jin</author><author>Cho,Kyoung-Oh</author><author>Nam,JongHee</author><author>Kim,Nacksung</author><author>Park,Young-Kyu</author><author>Bom,Hee-Seung</author><author>Rhee,JoonHaeng</author><author>Choy,HyonE.</author></authors></contributors><titles><title>NoninvasiveReal-timeImagingofTumorsandMetastasesUsingTumor-targetingLight-emittingEscherichiacoli</title><secondary-title>MolecularImagingandBiology</secondary-title></titles><periodical><full-title>MolecularImagingandBiology</full-title></periodical><pages>54-61</pages><volume>10</volume><number>1</number><dates><year>2008</year><pub-dates><date>2008/01/01</date></pub-dates></dates><isbn>1860-2002</isbn><urls><related-urls><url>/10.1007/s11307-007-0120-5</url></related-urls></urls><electronic-resource-num>10.1007/s11307-007-0120-5</electronic-resource-num></record></Cite></EndNote>[101]。细菌常作为药物载体靶向肿瘤ADDINEN.CITE<EndNote><Cite><Author>Hosseinidoust</Author><Year>2016</Year><RecNum>1379</RecNum><DisplayText><styleface="superscript">[15]</style></DisplayText><record><rec-number>1379</rec-number><foreign-keys><keyapp="EN"db-id="we95a2ppjztw2ler5pzv5vfkdetsataxd5fs"timestamp="1618051295">1379</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Hosseinidoust,Zeinab</author><author>Mostaghaci,Babak</author><author>Yasa,Oncay</author><author>Park,Byung-Wook</author><author>Singh,AjayVikram</author><author>Sitti,Metin</author></authors></contributors><titles><title>Bioengineeredandbiohybridbacteria-basedsystemsfordrugdelivery</title><secondary-title>AdvancedDrugDeliveryReviews</secondary-title></titles><periodical><full-title>AdvancedDrugDeliveryReviews</full-title></periodical><pages>27-44</pages><volume>106</volume><keywords><keyword>Bacteria</keyword><keyword>Engineered</keyword><keyword>Biohybrid</keyword><keyword>Microrobotics</keyword><keyword>Syntheticbiology</keyword><keyword>Genetherapy</keyword><keyword>Tumortargeting</keyword><keyword>Celltherapy</keyword><keyword>Microbialfactories</keyword><keyword>Bactofection</keyword></keywords><dates><year>2016</year><pub-dates><date>2016/11/15/</date></pub-dates></dates><isbn>0169-409X</isbn><urls><related-urls><url>/science/article/pii/S0169409X16302629</url></related-urls></urls><electronic-resource-num>/10.1016/j.addr.2016.09.007</electronic-resource-num></record></Cite></EndNote>[15],在靶向过程中,存在靶细胞对于细菌的吞噬ADDINEN.CITEADDINEN.CITE.DATA[15,102-104]。Bashir等人2017年报道了装载荧光、生物发光基因的PS球功能化的李斯特菌构建杂化细菌马达,该细菌马达可以在体外被多种肿瘤细胞内化吞噬ADDINEN.CITE<EndNote><Cite><Author>Park</Author><Year>2013</Year><RecNum>1361</RecNum><DisplayText><styleface="superscript">[81]</style></DisplayText><record><rec-number>1361</rec-number><foreign-keys><keyapp="EN"db-id="we95a2ppjztw2ler5pzv5vfkdetsataxd5fs"timestamp="1618039962">1361</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]。活体成像结果显示绿色荧光蛋白在小鼠体内成功转录和表达。由于细菌具有渗透进入肿瘤组织的能力,因此基于细菌的靶向系统具有良好的应用。Oliver课题组及Vanderlick等人提出了基于精子及细胞融合能力的靶向系统ADDINEN.CITE<EndNote><Cite><Author>Xu</Author><Year>2018</Year><RecNum>45</RecNum><DisplayText><styleface="superscript">[42]</style></DisplayText><record><rec-number>45</rec-number><foreign-keys><keyapp="EN"db-id="0v9arpfdqrxsp9esrsspdpw1f2sxvxz2552v"timestamp="1567963586">45</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Xu,Haifeng</author><author>Medina-Sánchez,Mariana</author><author>Magdanz,Veronika</author><author>Schwarz,Lukas</author><author>Hebenstreit,Franziska</author><author>Schmidt,OliverG.</author></authors></contributors><titles><title>Sperm-HybridMicromotorforTargetedDrugDelivery</title><secondary-title>ACSNano</secondary-title></titles><periodical><full-title>ACSNano</full-title></periodical><pages>327-337</pages><volume>12</volume><number>1</number><dates><year>2018</year><pub-dates><date>2018/01/23</date></pub-dates></dates><publisher>AmericanChemicalSociety</publisher><isbn>1936-0851</isbn><urls><related-urls><url>/10.1021/acsnano.7b06398</url></related-urls></urls><electronic-resource-num>10.1021/acsnano.7b06398</electronic-resource-num></record></Cite></EndNote>[42]。其中Vanderlick等人将囊泡附着在精子表面,不影响精子的生理和运动特性ADDINEN.CITE<EndNote><Cite><Author>Geerts</Author><Year>2014</Year><RecNum>1362</RecNum><DisplayText><styleface="superscript">[62]</style></DisplayText><record><rec-number>1362</rec-number><foreign-keys><keyapp="EN"db-id="we95a2ppjztw2ler5pzv5vfkdetsataxd5fs"timestamp="1618040651">1362</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Geerts,N.</author><author>McGrath,J.</author><author>Stronk,J.N.</author><author>Vanderlick,T.K.</author><author>Huszar,G.</author></authors></contributors><titles><title>Spermatozoaasatransportsystemoflargeunilamellarlipidvesiclesintotheoocyte</title><secondary-title>ReproductiveBioMedicineOnline</secondary-title></titles><periodical><full-title>ReproductiveBioMedicineOnline</full-title></periodical><pages>451-461</pages><volume>28</volume><number>4</number><keywords><keyword>lipidvesicles</keyword><keyword>mouse</keyword><keyword>spermatozoa</keyword><keyword>transport</keyword><keyword>delivery</keyword><keyword>hybrid</keyword></keywords><dates><year>2014</year><pub-dates><date>2014/04/01/</date></pub-dates></dates><isbn>1472-6483</isbn><urls><related-urls><url>/science/article/pii/S1472648313006251</url></related-urls></urls><electronic-resource-num>/10.1016/j.rbmo.2013.11.009</electronic-resource-num></record></Cite></EndNote>[62]。同时精子仍能与透明质酸结合,可以完成靶向运动,并仍然具有授精能力。杂化精子马达通过人工磁性组分与精子的结合,利用磁场操控人工组分,完成靶向运动ADDINEN.CITE<EndNote><Cite><Author>Magdanz</Author><Year>2013</Year><RecNum>34</RecNum><DisplayText><styleface="superscript">[63]</style></DisplayText><record><rec-number>34</rec-number><foreign-keys><keyapp="EN"db-id="0v9arpfdqrxsp9esrsspdpw1f2sxvxz2552v"timestamp="1567959234">34</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Magdanz,Veronika</author><author>Sanchez,Samuel</author><author>Schmidt,OliverG.</author></authors></contributors><titles><title>DevelopmentofaSperm-FlagellaDrivenMicro-Bio-Robot</title><secondary-title>AdvancedMaterials</secondary-title></titles><periodical><full-title>AdvancedMaterials</full-title></periodical><pages>6581-6588</pages><volume>25</volume><number>45</number><keywords><keyword>micro-bio-robot</keyword><keyword>motilecell</keyword><keyword>spermflagella</keyword><keyword>magneticcontrol</keyword><keyword>microtube</keyword></keywords><dates><year>2013</year><pub-dates><date>2013/12/01</date></pub-dates></dates><publisher>JohnWiley&Sons,Ltd</publisher><isbn>0935-9648</isbn><urls><related-urls><url>/10.1002/adma.201302544</url><url>/doi/full/10.1002/adma.201302544</url></related-urls></urls><electronic-resource-num>10.1002/adma.201302544</electronic-resource-num><access-date>2019/09/08</access-date></record></Cite></EndNote>[63]。2016年,Oliver课题组进一步使用人工方式,推进缺乏运动能力的精子,构建杂化精子马达,完成受精过程ADDINEN.CITE<EndNote><Cite><Author>Medina-Sánchez</Author><Year>2016</Year><RecNum>1365</RecNum><DisplayText><styleface="superscript">[17]</style></DisplayText><record><rec-number>1365</rec-number><foreign-keys><keyapp="EN"db-id="we95a2ppjztw2ler5pzv5vfkdetsataxd5fs"timestamp="1618041236">1365</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Medina-Sánchez,Mariana</author><author>Schwarz,Lukas</author><author>Meyer,AnneK.</author><author>Hebenstreit,Franziska</author><author>Schmidt,OliverG.</author></authors></contributors><titles><title>CellularCargoDelivery:TowardAssistedFertilizationbySperm-CarryingMicromotors</title><secondary-title>NanoLetters</secondary-title></titles><periodical><full-title>NanoLetters</full-title></periodical><pages>555-561</pages><volume>16</volume><number>1</number><dates><year>2016</year><pub-dates><date>2016/01/13</date></pub-dates></dates><publisher>AmericanChemicalSociety</publisher><isbn>1530-6984</isbn><urls><related-urls><url>/10.1021/acs.nanolett.5b04221</url></related-urls></urls><electronic-resource-num>10.1021/acs.nanolett.5b04221</electronic-resource-num></record></Cite></EndNote>[17]。Yang等报道了另一种操控杂化细胞马达运动的方法,将掺杂Fe3O4的海藻酸钠组装修饰至酵母细胞和细菌上,模拟细胞的趋磁性ADDINEN.CITE<EndNote><Cite><Author>Shi</Author><Year>2016</Year><RecNum>1366</RecNum><DisplayText><styleface="superscript">[105]</style></DisplayText><record><rec-number>1366</rec-number><foreign-keys><keyapp="EN"db-id="we95a2ppjztw2ler5pzv5vfkdetsataxd5fs"timestamp="1618041565">1366</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Shi,Xudian</author><author>Shi,Zhijun</author><author>Wang,Daming</author><author>Ullah,MuhammadWajid</author><author>Yang,Guang</author></authors></contributors><titles><title>MicrobialCellswithaFe3O4DopedHydrogelExtracellularMatrix:ManipulationofLivingCellsbyMagneticStimulus</title><secondary-title>MacromolecularBioscience</secondary-title></titles><periodical><full-title>MacromolecularBioscience</full-title></periodical><pages>1506-1514</pages><volume>16</volume><number>10</number><keywords><keyword>alginatehydrogel</keyword><keyword>hydrogelextracellularmatrix</keyword><keyword>magneticmodified</keyword><keyword>magneticnanoparticles</keyword><keyword>magneticstimulus</keyword></keywords><dates><year>2016</year><pub-dates><date>2016/10/01</date></pub-dates></dates><publisher>JohnWiley&Sons,Ltd</publisher><isbn>1616-5187</isbn><work-type>/10.1002/mabi.201600143</work-type><urls><related-urls><url>/10.1002/mabi.201600143</url></related-urls></urls><electronic-resource-num>/10.1002/mabi.201600143</electronic-resource-num><access-date>2021/04/10</access-date></record></Cite></EndNote>[105]。因此可以通过磁场实现对于杂化细胞马达的空间操纵,控制其靶向过程。Martel课题组通过趋向缺氧区域的趋磁细菌MC-1,同时通过外磁场控制和细菌自身对缺氧部位的靶向实现对肿瘤区域渗透和靶向药物递送ADDINEN.CITE<EndNote><Cite><Author>Martel</Author><Year>2006</Year><RecNum>1339</RecNum><DisplayText><styleface="superscript">[77]</style></DisplayText><record><rec-number>1339</rec-number><foreign-keys><keyapp="EN"db-id="we95a2ppjztw2ler5pzv5vfkdetsataxd5fs"timestamp="1617678848">1339</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Martel,Sylvain</author><author>Tremblay,CharlesC.</author><author>Ngakeng,Serge</author><author>Langlois,Guillaume</author></authors></contributors><titles><title>Controlledmanipulationandactuationofmicro-objectswithmagnetotacticbacteria</title><secondary-title>AppliedPhysicsLetters</secondary-title></titles><periodical><full-title>AppliedPhysicsLetters</full-title></periodical><pages>233904</pages><volume>89</volume><number>23</number><dates><year>2006</year><pub-dates><date>2006/12/04</date></pub-dates></dates><publisher>AmericanInstituteofPhysics</publisher><isbn>0003-6951</isbn><urls><related-urls><url>/10.1063/1.2402221</url></related-urls></urls><electronic-resource-num>10.1063/1.2402221</electronic-resource-num><access-date>2021/04/05</access-date></record></Cite></EndNote>[77]。针对肿瘤的治疗,Nguyen等人报道了一种基于鼠伤寒沙门氏菌的杂化细菌马达(如图1-14所示)ADDINEN.CITE<EndNote><Cite><Author>Nguyen</Author><Year>2016</Year><RecNum>1321</RecNum><DisplayText><styleface="superscript">[99]</style></DisplayText><record><rec-number>1321</rec-number><foreign-keys><keyapp="EN"db-id="we95a2ppjztw2ler5pzv5vfkdetsataxd5fs"timestamp="1617199338">1321</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Nguyen,VanDu</author><author>Han,Ji-Won</author><author>Choi,YoungJin</author><author>Cho,Sunghoon</author><author>Zheng,Shaohui</author><author>Ko,SeongYoung</author><author>Park,Jong-Oh</author><author>Park,Sukho</author></authors></contributors><titles><title>Activetumor-therapeuticliposomalbacteriobotcombiningadrug(paclitaxel)-encapsulatedliposomewithtargetingbacteria(SalmonellaTyphimurium)</title><secondary-title>SensorsandActuatorsB:Chemical</secondary-title></titles><periodical><full-title>SensorsandActuatorsB:Chemical</full-title></periodical><pages>217-224</pages><volume>224</volume><keywords><keyword>Liposome</keyword><keyword>Microrobot</keyword><keyword>Paclitaxel</keyword><keyword>Tumortherapy</keyword><keyword>Bacterialactuation</keyword></keywords><dates><year>2016</year><pub-dates><date>2016/03/01/</date></pub-dates></dates><isbn>0925-4005</isbn><urls><related-urls><url>/science/article/pii/S0925400515303415</url></related-urls></urls><electronic-resource-num>/10.1016/j.snb.2015.09.034</electronic-resource-num></record></Cite></EndNote>[99],如图1-15,将装载紫杉醇的脂质体与靶向肿瘤的鼠伤寒沙门氏菌结合,制备得到杂化细菌马达。杂化细菌马达显示出了相对纯脂质体更高的运动速度及更好的肿瘤细胞杀伤能力,可用于主动肿瘤治疗。Han等人报道了一种吞噬含磁性纳米颗粒和多烯紫杉醇的PLGA颗粒的杂化巨噬细胞马达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</a
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