《纳米药物递送系统分析》2800字

纳米药物递送系统分析综述传统的癌症治疗药物会分布到全身，包括肿瘤部位和正常组织，因此需要纳米载体改善抗肿瘤效果，减少对正常组织的毒副作用。现在，已经有许多类型的纳米粒被用作纳米药物递送系统（NDDS）。经过多年的发展，研究人员都认为NDDS具有突破生物屏障、改善靶点特性、提高肿瘤组织渗透能力等优点。PDT使用的光敏剂大多具有疏水性，且缺乏肿瘤选择性，SDT用到的声敏剂很多都是由光敏剂发展来的，具有相似的特性，而纳米载体能够增强体内循环时间且能控释释放，是一种良好的药物输送方式。1.1纳米药物输送载体1.1.1有机纳米输送载体（1）基于脂质的输送载体脂质体是由双层脂质形成的小型纳米泡，亲水药物可以被包裹在囊泡内，而疏水性的药物可，基于脂质的纳米粒子具有良好的生物相容性、生物降解性和低免疫原性等特征ADDINEN.CITEADDINEN.CITE.DATA[\o"Gao,2014#145"152]。除脂质体外，其他基于脂质的纳米载体还包括固体脂质纳米粒（Solidlipidnanoparticles）、纳米脂质载体（Nanostructuredlipidcarriers）、脂质药物结合体等类型ADDINEN.CITE<EndNote><Cite><Author>Alavi</Author><Year>2019</Year><RecNum>146</RecNum><DisplayText><styleface="superscript">[153]</style></DisplayText><record><rec-number>146</rec-number><foreign-keys><keyapp="EN"db-id="fefzva2arafxvjeezt3vr2rhx22ervre0wt2"timestamp="1618071842">146</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Alavi,M.</author><author>Hamidi,M.</author></authors></contributors><auth-address>DepartmentofNanobiotechnology,FacultyofScience,RaziUniversity,Kermanshah,Iran. ZanjanPharmaceuticalNanotechnologyResearchCenter(ZPNRC),Zanjan,Iran. DepartmentofPharmaceuticalNanotechnology,SchoolofPharmacy,ZanjanUniversityofMedicalSciences,Zanjan,Iran.</auth-address><titles><title>Passiveandactivetargetingincancertherapybyliposomesandlipidnanoparticles</title><secondary-title>DrugMetabPersTher</secondary-title></titles><periodical><full-title>DrugMetabPersTher</full-title></periodical><volume>34</volume><number>1</number><edition>2019/02/02</edition><keywords><keyword>AntineoplasticAgents/*administration&dosage/*therapeuticuse</keyword><keyword>Humans</keyword><keyword>Lipids/*administration&dosage</keyword><keyword>Liposomes</keyword><keyword>Nanoparticles/*administration&dosage/*chemistry</keyword><keyword>Neoplasms/*drugtherapy</keyword><keyword>*activetargeting</keyword><keyword>*cancertherapy</keyword><keyword>*lipidnanoparticles</keyword><keyword>*liposomes</keyword><keyword>*passivetargeting</keyword></keywords><dates><year>2019</year><pub-dates><date>Feb1</date></pub-dates></dates><isbn>2363-8915(Electronic) 2363-8915(Linking)</isbn><accession-num>30707682</accession-num><urls><related-urls><url>/pubmed/30707682</url></related-urls></urls><electronic-resource-num>10.1515/dmpt-2018-0032</electronic-resource-num></record></Cite></EndNote>[\o"Alavi,2019#146"153]。（2）基于聚合物的输送载体聚乳酸（PLA）是多种微生物产生的天然聚酯，可用作核苷酸、蛋白质和化疗药物的载体。PLA和磷脂膜具有相同的电荷，不会对磷脂膜造成破坏性威胁，其渗入细胞膜的机制有地毯模型、皮带模型和桶装模型。由于它产量低，成本高，还需要更进一步研究其合成生成才可促进它在生物药学的使用ADDINEN.CITEADDINEN.CITE.DATA[\o"Zhang,2021#213"154]。纳米凝胶是数十至数百纳米尺度的三维水凝胶颗粒，有聚合物通过物理或化学交联而成ADDINEN.CITE<EndNote><Cite><Author>Hamidi</Author><Year>2008</Year><RecNum>215</RecNum><DisplayText><styleface="superscript">[155]</style></DisplayText><record><rec-number>215</rec-number><foreign-keys><keyapp="EN"db-id="fefzva2arafxvjeezt3vr2rhx22ervre0wt2"timestamp="1618799760">215</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Hamidi,M.</author><author>Azadi,A.</author><author>Rafiei,P.</author></authors></contributors><auth-address>FacultyofPharmacy,ShirazUniversityofMedicalSciences,P.O.Box71345-1583,Shiraz,Iran.hamidim@sums.ac.ir</auth-address><titles><title>Hydrogelnanoparticlesindrugdelivery</title><secondary-title>AdvDrugDelivRev</secondary-title><alt-title>Advanceddrugdeliveryreviews</alt-title></titles><periodical><full-title>AdvDrugDelivRev</full-title></periodical><pages>1638-49</pages><volume>60</volume><number>15</number><edition>2008/10/09</edition><keywords><keyword>Animals</keyword><keyword>Cross-LinkingReagents/chemistry</keyword><keyword>*DrugDeliverySystems</keyword><keyword>Humans</keyword><keyword>Hydrogels/*administration&dosage/chemistry</keyword><keyword>HydrophobicandHydrophilicInteractions</keyword><keyword>*Nanoparticles</keyword><keyword>Polymers/chemistry</keyword></keywords><dates><year>2008</year><pub-dates><date>Dec14</date></pub-dates></dates><isbn>1872-8294(Electronic) 0169-409X(Linking)</isbn><accession-num>18840488</accession-num><urls><related-urls><url>/pubmed/18840488</url></related-urls></urls><electronic-resource-num>10.1016/j.addr.2008.08.002</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>[\o"Hamidi,2008#215"155]。化学交联凝胶具有非常稳定的网络结构，机械强度较高，可以通过交联程度、交联剂性质等改变制备可控孔径的交联凝胶。纳米凝胶的多种物理化学特性，比如尺寸、渗透性、含水量和亲水疏水性，都会虽pH值、温度等变化而变化，因此将其用作响应性纳米药物输送系统是可行的ADDINEN.CITEADDINEN.CITE.DATA[\o"Kuksenok,2014#217"156]。（3）基于蛋白多肽类的输送载体以蛋白质为基础的纳米输送载体通常具有良好的生物相容性、生物降解性和低毒性，可以由天然或合成的蛋白质与各种药物分子组合而成。已有许多研究报道用作化疗的热休克蛋白笼ADDINEN.CITEADDINEN.CITE.DATA[\o"Flenniken,2005#303"157]，参与前药设计的白蛋白ADDINEN.CITE<EndNote><Cite><Author>Kratz</Author><Year>2008</Year><RecNum>305</RecNum><DisplayText><styleface="superscript">[158]</style></DisplayText><record><rec-number>305</rec-number><foreign-keys><keyapp="EN"db-id="fefzva2arafxvjeezt3vr2rhx22ervre0wt2"timestamp="1620287265">305</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Kratz,F.</author></authors></contributors><auth-address>HeadofMacromolecularProdrugs,TumorBiologyCenter,BreisacherStrasse117,D-79106Freiburg,Germany.felix@tumorbio.uni-freiburg.de</auth-address><titles><title>Albuminasadrugcarrier:designofprodrugs,drugconjugatesandnanoparticles</title><secondary-title>JControlRelease</secondary-title><alt-title>Journalofcontrolledrelease:officialjournaloftheControlledReleaseSociety</alt-title></titles><periodical><full-title>JControlRelease</full-title></periodical><pages>171-83</pages><volume>132</volume><number>3</number><edition>2008/06/28</edition><keywords><keyword>Animals</keyword><keyword>BindingSites</keyword><keyword>BiologicalTransport</keyword><keyword>Chemistry,Pharmaceutical</keyword><keyword>*DrugCarriers</keyword><keyword>DrugCompounding</keyword><keyword>*DrugDesign</keyword><keyword>DrugStability</keyword><keyword>Half-Life</keyword><keyword>Humans</keyword><keyword>Models,Molecular</keyword><keyword>*Nanoparticles</keyword><keyword>Prodrugs/*chemistry/metabolism</keyword><keyword>ProteinConformation</keyword><keyword>SerumAlbumin/*chemistry/metabolism</keyword></keywords><dates><year>2008</year><pub-dates><date>Dec18</date></pub-dates></dates><isbn>1873-4995(Electronic) 0168-3659(Linking)</isbn><accession-num>18582981</accession-num><urls><related-urls><url>/pubmed/18582981</url></related-urls></urls><electronic-resource-num>10.1016/j.jconrel.2008.05.010</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>[\o"Kratz,2008#305"158]，以及放射免疫治疗中出现的铁蛋白载体ADDINEN.CITE<EndNote><Cite><Author>Wu</Author><Year>2008</Year><RecNum>307</RecNum><DisplayText><styleface="superscript">[159]</style></DisplayText><record><rec-number>307</rec-number><foreign-keys><keyapp="EN"db-id="fefzva2arafxvjeezt3vr2rhx22ervre0wt2"timestamp="1620287810">307</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Wu,H.</author><author>Wang,J.</author><author>Wang,Z.</author><author>Fisher,D.R.</author><author>Lin,Y.</author></authors></contributors><auth-address>PacificNorthwestNationalLaboratory,Richland,WA99352,USA.</auth-address><titles><title>Apoferritin-templatedyttriumphosphatenanoparticleconjugatesforradioimmunotherapyofcancers</title><secondary-title>JNanosciNanotechnol</secondary-title><alt-title>Journalofnanoscienceandnanotechnology</alt-title></titles><periodical><full-title>JNanosciNanotechnol</full-title><abbr-1>Journalofnanoscienceandnanotechnology</abbr-1></periodical><alt-periodical><full-title>JNanosciNanotechnol</full-title><abbr-1>Journalofnanoscienceandnanotechnology</abbr-1></alt-periodical><pages>2316-22</pages><volume>8</volume><number>5</number><edition>2008/06/25</edition><keywords><keyword>Apoferritins/*chemistry</keyword><keyword>Humans</keyword><keyword>*MetalNanoparticles</keyword><keyword>Microscopy,Electron,Transmission</keyword><keyword>Neoplasms/*radiotherapy</keyword><keyword>*Radioimmunotherapy</keyword><keyword>Yttrium/*chemistry</keyword></keywords><dates><year>2008</year><pub-dates><date>May</date></pub-dates></dates><isbn>1533-4880(Print) 1533-4880(Linking)</isbn><accession-num>18572643</accession-num><urls><related-urls><url>/pubmed/18572643</url></related-urls></urls><electronic-resource-num>10.1166/jnn.2008.177</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>[\o"Wu,2008#307"159]，它们具有良好的药代动力学性质，且稳定性也不错。1.1.2无机纳米输送载体常见的无机纳米输送载体有硅、金、银、铁等纳米粒子，还有一些纳米碳材料、量子点等，这些无机材料在药物输送、靶向给药以及肿瘤治疗等方面都显示出很好的应用前景。（1）介孔二氧化硅纳米粒介孔二氧化硅纳米粒（Mesoporoussilicananoparticle，MSN）在1992年首次被科学家报道ADDINEN.CITE<EndNote><Cite><Author>Kresge</Author><Year>1992</Year><RecNum>287</RecNum><DisplayText><styleface="superscript">[160]</style></DisplayText><record><rec-number>287</rec-number><foreign-keys><keyapp="EN"db-id="fefzva2arafxvjeezt3vr2rhx22ervre0wt2"timestamp="1619767819">287</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Kresge,C.T.</author><author>Leonowicz,M.E.</author><author>Roth,W.J.</author><author>Vartuli,J.C.</author><author>Beck,J.S.</author></authors></contributors><auth-address>MobilRes&DevCorp,CentResLab,Princeton,Nj08540</auth-address><titles><title>OrderedMesoporousMolecular-SievesSynthesizedbyaLiquid-CrystalTemplateMechanism</title><secondary-title>Nature</secondary-title><alt-title>Nature</alt-title></titles><periodical><full-title>Nature</full-title></periodical><alt-periodical><full-title>Nature</full-title></alt-periodical><pages>710-712</pages><volume>359</volume><number>6397</number><keywords><keyword>phosphate</keyword></keywords><dates><year>1992</year><pub-dates><date>Oct22</date></pub-dates></dates><isbn>0028-0836</isbn><accession-num>WOS:A1992JU65000049</accession-num><urls><related-urls><url><GotoISI>://WOS:A1992JU65000049</url></related-urls></urls><electronic-resource-num>DOI10.1038/359710a0</electronic-resource-num><language>English</language></record></Cite></EndNote>[\o"Kresge,1992#287"160]，这种介孔结构纳米粒引起了强烈的注意，当时它主要在离子交换、催化和吸附等领域彰显作用，直到2001年，它被研究人员用作NDDS的载体ADDINEN.CITE<EndNote><Cite><Author>Vallet-Regi</Author><Year>2000</Year><RecNum>289</RecNum><DisplayText><styleface="superscript">[161]</style></DisplayText><record><rec-number>289</rec-number><foreign-keys><keyapp="EN"db-id="fefzva2arafxvjeezt3vr2rhx22ervre0wt2"timestamp="1619768682">289</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Vallet-Regi,M.</author><author>Rámila,A.</author><author>delReal,R.P.</author><author>Pérez-Pariente,J.</author></authors></contributors><titles><title>ANewPropertyofMCM-41: DrugDeliverySystem</title><secondary-title>ChemistryofMaterials</secondary-title></titles><periodical><full-title>ChemistryofMaterials</full-title></periodical><pages>308-311</pages><volume>13</volume><number>2</number><section>308</section><dates><year>2000</year><pub-dates><date>2001/02/01</date></pub-dates></dates><publisher>AmericanChemicalSociety</publisher><isbn>0897-4756 1520-5002</isbn><urls><related-urls><url>/10.1021/cm0011559</url></related-urls></urls><electronic-resource-num>10.1021/cm0011559</electronic-resource-num></record></Cite></EndNote>[\o"Vallet-Regi,2000#289"161]，随后十多年它便作为药物输送载体在纳米药物的诊断与治疗领域大放异彩。MSN是一种相当独特的纳米材料，早已被用作NDDS。它具有粒径小、孔径可调、表面积大、生物相容性良好等优点。肿瘤治疗时的副作用始终是不可忽视的，而MSN的毒性低，生物降解性优良，一定程度上降低了药物输送载体的副作用。明确的介孔结构和独特的中空结构，高表面积，高孔体积和可调整的孔径，确保了MSN巨大的负载能力ADDINEN.CITE<EndNote><CiteExcludeYear="1"><Author>Mamaeva</Author><Year>2013</Year><RecNum>12</RecNum><DisplayText><styleface="superscript">[162]</style></DisplayText><record><rec-number>12</rec-number><foreign-keys><keyapp="EN"db-id="fefzva2arafxvjeezt3vr2rhx22ervre0wt2"timestamp="1585228401">12</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Mamaeva,V.</author><author>Sahlgren,C.</author><author>Linden,M.</author></authors></contributors><auth-address>TurkuCentreforBiotechnology,UniversityofTurkuandAboAkademiUniversity,P.O.Box123,FI-20521,Turku,Finland.</auth-address><titles><title>Mesoporoussilicananoparticlesinmedicine--recentadvances</title><secondary-title>AdvDrugDelivRev</secondary-title></titles><periodical><full-title>AdvDrugDelivRev</full-title></periodical><pages>689-702</pages><volume>65</volume><number>5</number><edition>2012/08/28</edition><keywords><keyword>Animals</keyword><keyword>DrugDeliverySystems/*methods</keyword><keyword>Humans</keyword><keyword>Nanoparticles/administration&dosage/*chemistry</keyword><keyword>Neoplasms/chemistry/drugtherapy/metabolism</keyword><keyword>ParticleSize</keyword><keyword>Phototherapy/methods</keyword><keyword>Porosity/drugeffects</keyword><keyword>SiliconDioxide/administration&dosage/*chemistry/metabolism</keyword><keyword>TissueDistribution/drugeffects/physiology</keyword></keywords><dates><year>2013</year><pub-dates><date>May</date></pub-dates></dates><isbn>1872-8294(Electronic) 0169-409X(Linking)</isbn><accession-num>22921598</accession-num><urls><related-urls><url>/pubmed/22921598</url></related-urls></urls><electronic-resource-num>10.1016/j.addr.2012.07.018</electronic-resource-num></record></Cite></EndNote>[\o"Mamaeva,2013#155"162]。同时，MSN易与其他功能材料通过表面涂层的方法杂交，获得新的理化特性ADDINEN.CITE<EndNote><CiteExcludeYear="1"><Author>Vivero-Escoto</Author><Year>2012</Year><RecNum>13</RecNum><DisplayText><styleface="superscript">[163]</style></DisplayText><record><rec-number>13</rec-number><foreign-keys><keyapp="EN"db-id="fefzva2arafxvjeezt3vr2rhx22ervre0wt2"timestamp="1585233282">13</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Vivero-Escoto,J.L.</author><author>Huxford-Phillips,R.C.</author><author>Lin,W.</author></authors></contributors><auth-address>DepartmentofChemistry,UniversityofNorthCarolinaatChapelHill,CB#390,ChapelHill,NorthCarolina27599,USA.</auth-address><titles><title>Silica-basednanoprobesforbiomedicalimagingandtheranosticapplications</title><secondary-title>ChemSocRev</secondary-title></titles><periodical><full-title>ChemSocRev</full-title></periodical><pages>2673-85</pages><volume>41</volume><number>7</number><edition>2012/01/12</edition><keywords><keyword>Animals</keyword><keyword>CellLine,Tumor</keyword><keyword>ContrastMedia/*chemicalsynthesis/chemistry</keyword><keyword>DiagnosticImaging</keyword><keyword>Mice</keyword><keyword>Nanoparticles/*chemistry</keyword><keyword>Porosity</keyword><keyword>SiliconDioxide/*chemistry</keyword></keywords><dates><year>2012</year><pub-dates><date>Apr7</date></pub-dates></dates><isbn>1460-4744(Electronic) 0306-0012(Linking)</isbn><accession-num>22234515</accession-num><urls><related-urls><url>/pubmed/22234515</url></related-urls></urls><custom2>PMC3777230</custom2><electronic-resource-num>10.1039/c2cs15229k</electronic-resource-num></record></Cite></EndNote>[\o"Vivero-Escoto,2012#156"163]，且其生物降解的速率还可以通过有机-无机杂交或金属离子掺杂等途径控制ADDINEN.CITEADDINEN.CITE.DATA[\o"Vivero-Escoto,2012#156"163,\o"Croissant,2017#157"164]。（2）其他无机纳米材料金纳米粒（AuNPs）是一种金属纳米粒，它可以被合成为各种形状，其中包括金纳米棒、三角形以及球形金纳米粒ADDINEN.CITEADDINEN.CITE.DATA[\o"Connor,2018#311"165]。AuNPs具有1~200nm可选择合成的尺寸，它的大小直接影响在体内的进程，比如小于100nm的AuNPs容易进入细胞内，小于20nm则可顺利穿透血管，而20~100nm的AuNPs更加安全，但也要考虑它的形状与表面修饰ADDINEN.CITE<EndNote><Cite><Author>Lewinski</Author><Year>2008</Year><RecNum>313</RecNum><DisplayText><styleface="superscript">[166]</style></DisplayText><record><rec-number>313</rec-number><foreign-keys><keyapp="EN"db-id="fefzva2arafxvjeezt3vr2rhx22ervre0wt2"timestamp="1620306569">313</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Lewinski,N.</author><author>Colvin,V.</author><author>Drezek,R.</author></authors></contributors><auth-address>DepartmentofBioengineeringMS-142,RiceUniversity,POBox1892,Houston,TX77251-1892,USA.</auth-address><titles><title>Cytotoxicityofnanoparticles</title><secondary-title>Small</secondary-title></titles><pages>26-49</pages><volume>4</volume><number>1</number><edition>2008/01/01</edition><keywords><keyword>Animals</keyword><keyword>Carbon/chemistry</keyword><keyword>CellSurvival/drugeffects</keyword><keyword>Humans</keyword><keyword>Metals/chemistry</keyword><keyword>Nanoparticles/chemistry/*toxicity</keyword><keyword>Semiconductors</keyword></keywords><dates><year>2008</year><pub-dates><date>Jan</date></pub-dates></dates><isbn>1613-6829(Electronic) 1613-6810(Linking)</isbn><accession-num>18165959</accession-num><urls><related-urls><url>/pubmed/18165959</url></related-urls></urls><electronic-resource-num>10.1002/smll.200700595</electronic-resource-num></record></Cite></EndNote>[\o"Lewinski,2008#313"166]。硫化铜可以通过热溶胶、气溶胶、溶液和热解等方法合成不同的形态和大小ADDINEN.CITE<EndNote><Cite><Author>Shamraiz</Author><Year>2016</Year><RecNum>210</RecNum><DisplayText><styleface="superscript">[167]</style></DisplayText><record><rec-number>210</rec-number><foreign-keys><keyapp="EN"db-id="fefzva2arafxvjeezt3vr2rhx22ervre0wt2"timestamp="1618797186">210</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Shamraiz,U.</author><author>Hussain,R.A.</author><author>Badshah,A.</author></authors></contributors><auth-address>QuaidIAzamUniv,DeptChem,Islamabad45320,Pakistan</auth-address><titles><title>Fabricationandapplicationsofcoppersulfide(CuS)nanostructures</title><secondary-title>JournalofSolidStateChemistry</secondary-title><alt-title>JSolidStateChem</alt-title></titles><periodical><full-title>JournalofSolidStateChemistry</full-title></periodical><pages>25-40</pages><volume>238</volume><keywords><keyword>chalcogenides</keyword><keyword>nanostructures</keyword><keyword>electronmicroscopy</keyword><keyword>x-raydiffraction</keyword><keyword>electricalconductivity</keyword><keyword>chemicalbathdeposition</keyword><keyword>hollowspheres</keyword><keyword>thin-films</keyword><keyword>solvothermalsynthesis</keyword><keyword>growth</keyword><keyword>electrodeposition</keyword><keyword>superstructures</keyword><keyword>nanoparticles</keyword><keyword>microspheres</keyword><keyword>degradation</keyword></keywords><dates><year>2016</year><pub-dates><date>Jun</date></pub-dates></dates><isbn>0022-4596</isbn><accession-num>WOS:000375635200005</accession-num><urls><related-urls><url><GotoISI>://WOS:000375635200005</url></related-urls></urls><electronic-resource-num>10.1016/j.jssc.2016.02.046</electronic-resource-num><language>English</language></record></Cite></EndNote>[\o"Shamraiz,2016#210"167]。硫化铜纳米载体因其可以在肝细胞代谢后通过肝胆排泄物清除，能迅速从体内消除，所以适合作为无机纳米载体的临床应用。Ding等人制备的聚乙二醇修饰的硫化铜纳米系统在Hela细胞中表现出良好的光声成像效果ADDINEN.CITE<EndNote><Cite><Author>Ding</Author><Year>2015</Year><RecNum>212</RecNum><DisplayText><styleface="superscript">[168]</style></DisplayText><record><rec-number>212</rec-number><foreign-keys><keyapp="EN"db-id="fefzva2arafxvjeezt3vr2rhx22ervre0wt2"timestamp="1618797823">212</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Ding,K.</author><author>Zeng,J.</author><author>Jing,L.</author><author>Qiao,R.</author><author>Liu,C.</author><author>Jiao,M.</author><author>Li,Z.</author><author>Gao,M.</author></authors></contributors><auth-address>InstituteofChemistry,ChineseAcademyofSciences,BeiYiJie2,ZhongGuanCun,Beijing100190,China.gaomy@qiaorr@.</auth-address><titles><title>AqueoussynthesisofPEGylatedcoppersulfidenanoparticlesforphotoacousticimagingoftumors</title><secondary-title>Nanoscale</secondary-title></titles><periodical><full-title>Nanoscale</full-title></periodical><pages>11075-81</pages><volume>7</volume><number>25</number><edition>2015/06/10</edition><keywords><keyword>Animals</keyword><keyword>CellSurvival/drugeffects</keyword><keyword>Copper/*chemistry</keyword><keyword>HeLaCells</keyword><keyword>Humans</keyword><keyword>Male</keyword><keyword>MetalNanoparticles/*chemistry</keyword><keyword>Mice</keyword><keyword>Mice,InbredBALBC</keyword><keyword>Nanotechnology</keyword><keyword>PhotoacousticTechniques/*methods</keyword><keyword>PolyethyleneGlycols</keyword><keyword>Sulfides/*chemistry</keyword></keywords><dates><year>2015</year><pub-dates><date>Jul7</date></pub-dates></dates><publisher>TheRoyalSocietyofChemistry</publisher><isbn>2040-3372(Electronic) 2040-3364(Linking)</isbn><accession-num>26055816</accession-num><work-type>10.1039/C5NR02180D</work-type><urls><related-urls><url>/pubmed/26055816</url></related-urls></urls><electronic-resource-num>10.1039/c5nr02180d</electronic-resource-num></record></Cite></EndNote>[\o"Ding,2015#212"168]。1.2肿瘤的靶向递送化疗药不具有肿瘤选择性，因此导致全身毒性，为了特异性针对肿瘤细胞或实体瘤，研究人员的目光放在了研究肿瘤的生理病理特点以寻找生物标记物，并将其用与纳米药物输送载体的靶向递药。（1）被动靶向在实体瘤中，纳米药物可以通过增强的渗透性和滞留效应（EPR效应）增加肿瘤积累。1986年，Matsumura首次提出了EPR效应的概念ADDINEN.CITE<EndNote><Cite><Author>Matsumura</Author><Year>1986</Year><RecNum>220</RecNum><DisplayText><styleface="superscript">[169]</style></DisplayText><record><rec-number>220</rec-number><foreign-keys><keyapp="EN"db-id="fefzva2arafxvjeezt3vr2rhx22ervre0wt2"timestamp="1618817688">220</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Matsumura,Y.</author><author>Maeda,H.</author></authors></contributors><titles><title>Anewconceptformacromoleculartherapeuticsincancerchemotherapy:mechanismoftumoritropicaccumulationofproteinsandtheantitumoragentsmancs</title><secondary-title>CancerRes</secondary-title><alt-title>Cancerresearch</alt-title></titles><periodical><full-title>CancerRes</full-title></periodical><pages>6387-92</pages><volume>46</volume><number>12Pt1</number><edition>1986/12/01</edition><keywords><keyword>Albumins/metabolism</keyword><keyword>Animals</keyword><keyword>Antibiotics,Antineoplastic/*metabolism</keyword><keyword>AntineoplasticAgents/*metabolism/therapeuticuse</keyword><keyword>EvansBlue/metabolism</keyword><keyword>Furans/*metabolism</keyword><keyword>MaleicAnhydrides/*metabolism/therapeuticuse</keyword><keyword>MetabolicClearanceRate</keyword><keyword>Mice</keyword><keyword>MolecularWeight</keyword><keyword>Neoplasms,Experimental/drugtherapy/*metabolism</keyword><keyword>Polystyrenes/*metabolism/therapeuticuse</keyword><keyword>Proteins/*metabolism</keyword><keyword>Zinostatin/analogs&derivatives/*metabolism/therapeuticuse</keyword></keywords><dates><year>1986</year><pub-dates><date>Dec</date></pub-dates></dates><isbn>0008-5472(Print) 0008-5472(Linking)</isbn><accession-num>2946403</accession-num><urls><related-urls><url>/pubmed/2946403</url></related-urls></urls><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>[\o"Matsumura,1986#220"169]。调节VEGF信号、使用TNF-α、NO等都能够促进EPR效应ADDINEN.CITEADDINEN.CITE.DATA[\o"Fang,2011#224"170,\o"Bae,2011#226"171]。影响EPR的因素包肿瘤大小、类型和位置，功能淋巴结存在或缺失以及巨噬细胞肿瘤渗透的程度。局部激活的PDT在一定程度上促进了EPR效应ADDINEN.CITEADDINEN.CITE.DATA[\o"Chen,2006#228"172]。此外，在超声成像或治疗中，超声导致的声孔效应令脂质渗透性增加，临床试验也提示着该声孔效应突破血脑屏障的功效ADDINEN.CITEADDINEN.CITE.DATA[\o"Guvener,2017#230"173-175]。然而EPR介导的肿瘤部位积累在人类中远不如动物模型明显。（2）主动靶向由于肿瘤异质性，每个癌症患者最好的治疗方式需要量身定做。为了实现这种目的，靶向配体被连接到各种治疗或成像剂上，各式各样的靶向配体能够选择性识别并结合到肿瘤细胞上ADDINEN.CITE<EndNote><Cite><Author>Srinivasarao</Author><Year>2015</Year><RecNum>218</RecNum><DisplayText><styleface="superscript">[176]</style></DisplayText><record><rec-number>218</rec-number><foreign-keys><keyapp="EN"db-id="fefzva2arafxvjeezt3vr2rhx22ervre0wt2"timestamp="1618816774">218</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Srinivasarao,M.</author><author>Galliford,C.V.</author><author>Low,P.S.</author></authors></contributors><auth-address>DepartmentofChemistry,720ClinicDrive,PurdueUniversity,WestLafayette,Indiana47907,USA.</auth-address><titles><title>Principlesinthedesignofligand-targetedcancertherapeuticsandimagingagents</title><secondary-title>NatRevDrugDiscov</secondary-title></titles><periodical><full-title>NatRevDrugDiscov</full-title></periodical><pages>203-19</pages><volume>14</volume><number>3</number><edition>2015/02/24</edition><keywords><keyword>Animals</keyword><keyword>AntineoplasticAgents/*chemicalsynthesis/*pharmacology</keyword><keyword>ContrastMedia/*chemicalsynthesis/*pharmacology</keyword><keyword>DrugDeliverySystems</keyword><keyword>*DrugDesign</keyword><keyword>Humans</keyword><keyword>Ligands</keyword><keyword>Neoplasms/*diagnosis/*drugtherapy</keyword></keywords><dates><year>2015</year><pub-dates><date>Mar</date></pub-dates></dates><isbn>1474-1784(Electronic) 1474-1776(Linking)</isbn><accession-num>25698644</accession-num><urls><related-urls><url>/pubmed/25698644</url></related-urls></urls><electronic-resource-num>10.1038/nrd4519</electronic-resource-num></record></Cite></EndNote>[\o"Srinivasarao,2015#218"176]。目前被研究的主动靶向的配体有小分子化合物（如叶酸、半乳糖）、抗体、适配体等。抗体在肿瘤治疗中广为人知的一种用法是抗体-药物偶联物（Antibody-drugconjugate，ADC）ADDINEN.CITE<EndNote><Cite><Author>Ornes</Author><Year>2013</Year><RecNum>300</RecNum><DisplayText><styleface="superscript">[177]</style></DisplayText><record><rec-number>300</rec-number><foreign-keys><keyapp="EN"db-id="fefzva2arafxvjeezt3vr2rhx22ervre0wt2"timestamp="1620284458">300</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Ornes,S.</author></authors></contributors><titles><title>Antibody-drugconjugates</title><secondary-title>ProcNatlAcadSciUSA</secondary-title><alt-title>ProceedingsoftheNationalAcademyofSciencesoftheUnitedStatesofAmerica</alt-title></titles><periodical><full-title>ProcNatlAcadSciUSA</full-title></periodical><pages>13695</pages><volume>110</volume><number>34</number><edition>2013/08/22</edition><keywords><keyword>Antibodies,Monoclonal/chemistry/*metabolism</keyword><keyword>BrentuximabVedotin</keyword><keyword>DrugDeliverySystems/*trends</keyword><keyword>Humans</keyword><keyword>Immunoconjugates/*metabolism</keyword><keyword>PharmaceuticalPreparations/*metabolism</keyword></keywords><dates><year>2013</year><pub-dates><date>Aug20</date></pub-dates></dates><isbn>1091-6490(Electronic) 0027-8424(Linking)</isbn><accession-num>23964113</acc