納米藥物遞送系統(tǒng)分析綜述傳統(tǒng)的癌癥治療藥物會分布到全身，包括腫瘤部位和正常組織，因此需要納米載體改善抗腫瘤效果，減少對正常組織的毒副作用?，F(xiàn)在，已經(jīng)有許多類型的納米粒被用作納米藥物遞送系統(tǒng)（NDDS）。經(jīng)過多年的發(fā)展，研究人員都認為NDDS具有突破生物屏障、改善靶點特性、提高腫瘤組織滲透能力等優(yōu)點。PDT使用的光敏劑大多具有疏水性，且缺乏腫瘤選擇性，SDT用到的聲敏劑很多都是由光敏劑發(fā)展來的，具有相似的特性，而納米載體能夠增強體內(nèi)循環(huán)時間且能控釋釋放，是一種良好的藥物輸送方式。1.1納米藥物輸送載體1.1.1有機納米輸送載體（1）基于脂質(zhì)的輸送載體脂質(zhì)體是由雙層脂質(zhì)形成的小型納米泡，親水藥物可以被包裹在囊泡內(nèi)，而疏水性的藥物可，基于脂質(zhì)的納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]。除脂質(zhì)體外，其他基于脂質(zhì)的納米載體還包括固體脂質(zhì)納米粒（Solidlipidnanoparticles）、納米脂質(zhì)載體（Nanostructuredlipidcarriers）、脂質(zhì)藥物結(jié)合體等類型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）基于聚合物的輸送載體聚乳酸（PLA）是多種微生物產(chǎn)生的天然聚酯，可用作核苷酸、蛋白質(zhì)和化療藥物的載體。PLA和磷脂膜具有相同的電荷，不會對磷脂膜造成破壞性威脅，其滲入細胞膜的機制有地毯模型、皮帶模型和桶裝模型。由于它產(chǎn)量低，成本高，還需要更進一步研究其合成生成才可促進它在生物藥學的使用ADDINEN.CITEADDINEN.CITE.DATA[\o"Zhang,2021#213"154]。納米凝膠是數(shù)十至數(shù)百納米尺度的三維水凝膠顆粒，有聚合物通過物理或化學交聯(lián)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]?；瘜W交聯(lián)凝膠具有非常穩(wěn)定的網(wǎng)絡(luò)結(jié)構(gòu)，機械強度較高，可以通過交聯(lián)程度、交聯(lián)劑性質(zhì)等改變制備可控孔徑的交聯(lián)凝膠。納米凝膠的多種物理化學特性，比如尺寸、滲透性、含水量和親水疏水性，都會雖pH值、溫度等變化而變化，因此將其用作響應(yīng)性納米藥物輸送系統(tǒng)是可行的ADDINEN.CITEADDINEN.CITE.DATA[\o"Kuksenok,2014#217"156]。（3）基于蛋白多肽類的輸送載體以蛋白質(zhì)為基礎(chǔ)的納米輸送載體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質(zhì)與各種藥物分子組合而成。已有許多研究報道用作化療的熱休克蛋白籠ADDINEN.CITEADDINEN.CITE.DATA[\o"Flenniken,2005#303"157]，參與前藥設(shè)計的白蛋白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]，以及放射免疫治療中出現(xiàn)的鐵蛋白載體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]，它們具有良好的藥代動力學性質(zhì)，且穩(wěn)定性也不錯。1.1.2無機納米輸送載體常見的無機納米輸送載體有硅、金、銀、鐵等納米粒子，還有一些納米碳材料、量子點等，這些無機材料在藥物輸送、靶向給藥以及腫瘤治療等方面都顯示出很好的應(yīng)用前景。（1）介孔二氧化硅納米粒介孔二氧化硅納米粒（Mesoporoussilicananoparticle，MSN）在1992年首次被科學家報道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]，這種介孔結(jié)構(gòu)納米粒引起了強烈的注意，當時它主要在離子交換、催化和吸附等領(lǐng)域彰顯作用，直到2001年，它被研究人員用作NDDS的載體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]，隨后十多年它便作為藥物輸送載體在納米藥物的診斷與治療領(lǐng)域大放異彩。MSN是一種相當獨特的納米材料，早已被用作NDDS。它具有粒徑小、孔徑可調(diào)、表面積大、生物相容性良好等優(yōu)點。腫瘤治療時的副作用始終是不可忽視的，而MSN的毒性低，生物降解性優(yōu)良，一定程度上降低了藥物輸送載體的副作用。明確的介孔結(jié)構(gòu)和獨特的中空結(jié)構(gòu)，高表面積，高孔體積和可調(diào)整的孔徑，確保了MSN巨大的負載能力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]。同時，MSN易與其他功能材料通過表面涂層的方法雜交，獲得新的理化特性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還可以通過有機-無機雜交或金屬離子摻雜等途徑控制ADDINEN.CITEADDINEN.CITE.DATA[\o"Vivero-Escoto,2012#156"163,\o"Croissant,2017#157"164]。（2）其他無機納米材料金納米粒（AuNPs）是一種金屬納米粒，它可以被合成為各種形狀，其中包括金納米棒、三角形以及球形金納米粒ADDINEN.CITEADDINEN.CITE.DATA[\o"Connor,2018#311"165]。AuNPs具有1~200nm可選擇合成的尺寸，它的大小直接影響在體內(nèi)的進程，比如小于100nm的AuNPs容易進入細胞內(nèi)，小于20nm則可順利穿透血管，而20~100nm的AuNPs更加安全，但也要考慮它的形狀與表面修飾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]。硫化銅可以通過熱溶膠、氣溶膠、溶液和熱解等方法合成不同的形態(tài)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]。硫化銅納米載體因其可以在肝細胞代謝后通過肝膽排泄物清除，能迅速從體內(nèi)消除，所以適合作為無機納米載體的臨床應(yīng)用。Ding等人制備的聚乙二醇修飾的硫化銅納米系統(tǒng)在Hela細胞中表現(xiàn)出良好的光聲成像效果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腫瘤的靶向遞送化療藥不具有腫瘤選擇性，因此導致全身毒性，為了特異性針對腫瘤細胞或?qū)嶓w瘤，研究人員的目光放在了研究腫瘤的生理病理特點以尋找生物標記物，并將其用與納米藥物輸送載體的靶向遞藥。（1）被動靶向在實體瘤中，納米藥物可以通過增強的滲透性和滯留效應(yīng)（EPR效應(yīng)）增加腫瘤積累。1986年，Matsumura首次提出了EPR效應(yīng)的概念A(yù)DDINEN.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]。調(diào)節(jié)VEGF信號、使用TNF-α、NO等都能夠促進EPR效應(yīng)ADDINEN.CITEADDINEN.CITE.DATA[\o"Fang,2011#224"170,\o"Bae,2011#226"171]。影響EPR的因素包腫瘤大小、類型和位置，功能淋巴結(jié)存在或缺失以及巨噬細胞腫瘤滲透的程度。局部激活的PDT在一定程度上促進了EPR效應(yīng)ADDINEN.CITEADDINEN.CITE.DATA[\o"Chen,2006#228"172]。此外，在超聲成像或治療中，超聲導致的聲孔效應(yīng)令脂質(zhì)滲透性增加，臨床試驗也提示著該聲孔效應(yīng)突破血腦屏障的功效ADDINEN.CITEADDINEN.CITE.DATA[\o"Guvener,2017#230"173-175]。然而EPR介導的腫瘤部位積累在人類中遠不如動物模型明顯。（2）主動靶向由于腫瘤異質(zhì)性，每個癌癥患者最好的治療方式需要量身定做。為了實現(xiàn)這種目的，靶向配體被連接到各種治療或成像劑上，各式各樣的靶向配體能夠選擇性識別并結(jié)合到腫瘤細胞上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]。目前被研究的主動靶向的配體有小分子化合物（如葉酸、半乳糖）、抗體、適配體等?？贵w在腫瘤治療中廣為人知的一種用法是抗體-藥物偶聯(lián)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