English
往期目录
新闻公告
More
化学进展 2019, Vol. 31 Issue (6): 783-790 DOI: 10.7536/PC181029   后一篇

• •

纳米金属有机框架材料在药物递送领域的应用

赖欣宜, 王志勇**(), 郑永太, 陈永明**()   

  1. 中山大学 聚合物复合材料及功能材料教育部重点实验室 材料科学与工程学院 广州 510275
  • 收稿日期:2018-10-22 出版日期:2019-06-15 发布日期:2019-04-26
  • 通讯作者: 王志勇, 陈永明
  • 基金资助:
    国家自然科学基金项目(51503230); 国家自然科学基金项目(81471778); 国家自然科学基金项目(51203177); 广东省引进创新创业团队项目(2013S086); 广州市科技计划项目(201804010101)
Richhtml ( 47 ) 下载PDF ( 1110 ) 引用
导出 被引次数 ( 2 )

Nanoscale Metal Organic Frameworks for Drug Delivery

Xinyi Lai, Zhiyong Wang**(), Yongtai Zheng, Yongming Chen**()   

  1. School of Materials Science and Engineering, Key Laboratory of Polymeric Composite Materials and Functional Materials of Ministry of Education, Sun Yat-sen University, Guangzhou 510275, China
  • Received:2018-10-22 Online:2019-06-15 Published:2019-04-26
  • Contact: Zhiyong Wang, Yongming Chen
  • About author:
    ** E-mail: (Zhiyong Wang);
    (Yongming Chen)
  • Supported by:
    National Natural Science Foundation of China(51503230); National Natural Science Foundation of China(81471778); National Natural Science Foundation of China(51203177); Guangdong Innovative and Entrepreneurial Research Team Program(2013S086); Science and Technology Program of Guangzhou,China(201804010101)

金属有机框架材料(Metal-Organic Frameworks, MOFs)是一类由金属离子及有机配体自组装而成的多孔材料,具有孔隙率高、比表面积大和结构多样化等独特优点,广泛应用于气体储存、物质分离和催化等领域。纳米尺寸金属有机框架材料(Nanoscale Metal-Organic Frameworks, NMOFs)既保持了传统MOFs的规整性,也具有纳米颗粒的特殊性质,在生物医药领域中是绝佳的药物载体。相比于传统纳米药物载体,NMOFs与药物的结合方式丰富,展现了多种药物装载模式,可以满足不同药物的制备需求,也可引入不同功能分子优化性能。最近,有越来越多的研究报道了多功能化NMOFs应用于药物递送领域,并实现刺激响应性的可控释放。本文将着重对NMOFs材料作为药物载体负载抗癌药物、光敏剂和核酸的应用进展进行综述。

关键词： 金属有机框架材料, 纳米颗粒, 药物递送, 抗癌药物, 光敏剂, 核酸

Metal-organic frameworks(MOFs), a class of self-assembled porous materials with metal ions and organic ligands, have attracted increasing research attention owing to their high porosity, tunable pore size, large surface area and multiple structures. In recent years, MOFs have been extensively investigated in gas storage, separation, catalysis and other fields. When the size of these hybrid materials drops down to nanosized scale, the regular morphology and unique properties make NMOFs become promising candidates for drug delivery. Compared to other nanocarriers, NMOFs provide multiple binding sites for a variety of small-molecule drugs and biomacromolecule via inclusion or surface conjugation. These chemical modifications do not affect NMOFs' intrinsic physicochemical properties. Moreover, the facile synthesis and mild preparation conditions endow NMOFs with advantages in biomedicine. Nowadays, NMOFs have been demonstrated with multifunctionalities and stimuli-responsive controlled release in vivo. Therefore, a detailed review of the application of NMOFs in controlled drug delivery of anticancer drugs, photosensitizer and nucleic acids is provided here.

Key words: metal-organic frameworks(MOFs), nanoparticle, drug delivery, anticancer drug, photosensitizer, nucleic acid
()
图1 脂质体及PEG包裹NMOF流程示意图[20]
Fig. 1 Schematic showing the general procedure for the NMOF with lipid and PEG coating[20].Copyright 2014, the Royal Society of Chemistry
图2 PDA-PCM@ZIF-8/DOX合成路线及可控热疗与化疗示意图。(a) 光照条件下不同pH环境中PDA-PCM@ZIF-8/DOX阿霉素释放曲线;(b) 由近红外光引发的PDA@ZIF-8/DOX及PDA-PCM@ZIF-8/DOX在相同pH条件下的阿霉素释放曲线区别[23]
Fig. 2 The synthesis of PDA-PCM@ZIF-8/DOX and controllable combined thermo-chemotherapy.(a) Controlled DOX release behaviors of the PDA-PCM@ZIF-8/DOX at different pH under NIR irradiation.(b) Controlled DOX release behaviors of the PDA@ZIF-8/DOX and PDA-PCM@ZIF-8/DOX at same pH under 37 ℃ shaking with additional 5 min NIR irradiation or not[23]. Copyright 2018, Elsevier
图3 PCN-224结构示意图:(a) Zr6金属簇、H2TCPP配体及PCN-224的3D纳米孔洞结构;(b) PCN-224立方体单元,及其组成的不同尺寸球形纳米颗粒示意图;(c)90 nm-PCN-224在不同激光条件下杀伤HeLa细胞效果对比;(d)1/4FA-PCN-224与PCN-224体外光动力治疗效果区别[30]
Fig. 3 Illustration of PCN-224 structure.(a) six-connected Zr6 cluster(Zr6O4(OH)4(H2O)6(OH)6(COO)6), tetratopic linker(tetrakis(4-carboxyphenyl)porphyrin(H2TCPP)), and 3D nanoporous framework of PCN-224.(b) A cubic unit of PCN-224 and schematic illustration of spherical PCN-224 nanoparticles on the basis of construction of cubic units, yielding different sizes.(c) Control experiments of cytotoxicity in HeLa cells upon light irradiation of 420 and 630 nm in the absence and presence of 90 nm-PCN-224. Irradiation time=30 min.(d) Comparison of in vitro PDT efficacy of pristine 1/4FA-PCN-224and PCN-224 in HeLa cells[30]. Copyright 2016, American Chemical Society
图4 (A) O2@UiO-66@ICG@RBC制备流程示意图;(B) 近红外激光促发O2释放及增强PDT治疗效果机理示意图[32]
Fig. 4 (A) Schematic illustration for preparation of O2@UiO-66@ICG@RBC.(B) Schematic illustration of NIR-triggered O2 releasing and enhanced PDT mechanism[32]. Copyright 2018, Elsevier
图5 通过破坏MCF-7/Taxol耐药株微管引起的逆转耐药性及凋亡诱导机理示意图[39]
Fig. 5 Mechanism of the reversal of drug resistance and induced apoptosis by the disruption of microtubule in MCF-7/T(Taxol-Resistance) Cancer Cells[39]. Copyright 2017, American Chemical Society
图6 UiO-66-N3纳米颗粒复合DNA流程示意图:(A) UiO-66-N3合成路线;(B) DBCO功能化DNA与UiO-66-N3的复合;(C) 菌株催化下MOF配体与DNA的点击反应[43]
Fig. 6 Synthesis and DNA Functionalization of UiO-66-N3 Nanoparticles.(A) Synthesis of UiO-66-N3(Zr6O4OH4(C8H3O4-N3)6) nano-particles.(B) DNA functionalization of UiO-66-N3 nanoparticles, utilizing DNA functionalized with DBCO.(C) Strain promoted click reaction between a MOF strut and DNA. Zirconium atoms=blue; oxygen atoms=red; carbon atoms=black; azide groups=green. Hydrogen atoms are omitted for clarity[43]. Copyright 2014, American Chemical Society
图7 ssDNA和MOF之间相互作用调控:(a) ssDNA负载在MOF精确可控孔径中的示意图;(b) 随MOF孔径增大,其与ssDNA间作用力逐渐增强,相对较弱的作用力既保证了ssDNA的高效负载和有效保护,又可实现其可逆释放[44]
Fig. 7 Fine-tuning of interactions between ssDNA and MOFs.(a) Illustration of ssDNA inclusion in MOFs composed of bio-compatible organic linkers and with precisely controlled pore sizes.(b) Gradual increase of interaction between ssDNA and MOFs as the pore size of MOF extended progressively. Relatively mild interactions guarantee the uptake and protection of ssDNA in the MOF pores, and also provide reversibility for their release[44]. Copyright 2018, Nature Publishing Group
[1]
Della R J, Liu D, Lin W . J. Shanghai Norm. Univ., 2012,44(10):957.
[2]
Yaghi O M, Li H, Davis C, Richardson D, Groy T L . Acc. Chem. Res., 1998,31(8):474.
[3]
Li H, Eddaoudi M, O’Keeffe M, Yaghi O M . Nature, 1999,402(6759):276.
[4]
Furukawa H, Yaghi O M . ChemInform, 2013,44(45):974.
[5]
Chen B, Xiang S, Qian G . Acc. Chem. Res., 2010,43(8):1115. https://www.ncbi.nlm.nih.gov/pubmed/20450174

doi: 10.1021/ar100023y     URL     pmid: 20450174
[6]
Liu J, Chen L, Cui H, Zhang J, Zhang L, Su C Y . Chem. Soc. Rev., 2014,43(16):6011. https://www.ncbi.nlm.nih.gov/pubmed/24871268

doi: 10.1039/c4cs00094c     URL     pmid: 24871268
[7]
Wang C, Liu D, Lin W . J. Am. Chem. Soc., 2013,135(36):13222. https://www.ncbi.nlm.nih.gov/pubmed/23944646

doi: 10.1021/ja308229p     URL     pmid: 23944646
[8]
Horcajada P, Serre C, Vallet-Regi M, Sebban M, Taulelle F, Ferey G . Angew. Chem.-Int. Ed., 2006,45(36):5974.
[9]
Davis M E, Chen Z, Shin D M . Nat. Rev. Drug Discov., 2008,7(9):771. https://www.ncbi.nlm.nih.gov/pubmed/18758474

doi: 10.1038/nrd2614     URL     pmid: 18758474
[10]
Taylor-Pashow K M L, Della Rocca J, Xie Z, Tran S, Lin W . J. Am. Chem. Soc., 2009,131(40):14261. https://www.ncbi.nlm.nih.gov/pubmed/19807179

doi: 10.1021/ja906198y     URL     pmid: 19807179
[11]
Liu J, Yang Y, Zhu W, Yi X, Dong Z, Xu X, Chen M, Yang K, Lu G, Jiang L, Liu Z . Biomaterials, 2016,97 1. https://www.ncbi.nlm.nih.gov/pubmed/27155362

doi: 10.1016/j.biomaterials.2016.04.034     URL     pmid: 27155362
[12]
Lu K, He C, Lin W . J. Am. Chem. Soc., 2014,136(48):16712. https://www.ncbi.nlm.nih.gov/pubmed/25407895

doi: 10.1021/ja508679h     URL     pmid: 25407895
[13]
Zhang L, Lei J, Ma F, Ling P, Liu J, Ju H . Chem. Commun., 2015,51(54):10831. https://www.ncbi.nlm.nih.gov/pubmed/26051476

doi: 10.1039/c5cc03028e     URL     pmid: 26051476
[14]
García-Uriostegui L, Meléndez-Ortiz H I, Toriz G, Delgado E . Mater. Lett., 2017,196 26.
[15]
Fang Q, Wang J, Gu S, Kaspar R B, Zhuang Z, Zheng J, Guo H, Qiu S, Yan Y . J. Am. Chem. Soc., 2015,137(26):8352. https://www.ncbi.nlm.nih.gov/pubmed/26099722

doi: 10.1021/jacs.5b04147     URL     pmid: 26099722
[16]
Horcajada P, Gref R, Baati T, Allan PK, Maurin G, Couvreur P, Ferey G, Morris R E, Serre C . Chem. Rev., 2012,112(2):1232. https://www.ncbi.nlm.nih.gov/pubmed/22168547

doi: 10.1021/cr200256v     URL     pmid: 22168547
[17]
Tamames-Tabar C, Cunha D, Imbuluzqueta E, Ragon F, Serre C, Blanco-Prieto M J, Horcajada P . J. Mater. Chem. B, 2014,2(3):262. https://www.ncbi.nlm.nih.gov/pubmed/32261505

doi: 10.1039/c3tb20832j     URL     pmid: 32261505
[18]
Rieter W J, Pott K M, Taylor K M L, Lin W .J. Am. Chem. Soc., 2008,130(35):11584.
[19]
Filippousi M, Turner S, Leus K, Siafaka P I, Tseligka E D, Vandichel M, Nanaki S G, Vizirianakis I S, Bikiaris D N, Van Der Voort P, Van Tendeloo G . Int. J. Pharm., 2016,509(1):208.
[20]
Liu D, He C, Poon C, Lin W . J. Mater. Chem. B, 2014,2(46):8249. https://www.ncbi.nlm.nih.gov/pubmed/32262098

doi: 10.1039/c4tb00751d     URL     pmid: 32262098
[21]
Ganta S, Devalapally H, Shahiwala A, Amiji M . J. Controlled Release, 2008,126(3):187. https://linkinghub.elsevier.com/retrieve/pii/S0168365908000254

doi: 10.1016/j.jconrel.2007.12.017     URL    
[22]
Shenoy D, Little S, Langer R, Amiji M . Pharm. Res., 2005,22(12):2107. https://www.ncbi.nlm.nih.gov/pubmed/16254763

doi: 10.1007/s11095-005-8343-0     URL     pmid: 16254763
[23]
Wu Q, Niu M, Chen X, Tan L, Fu C, Ren X, Ren J, Li L, Xu K, Zhong H, Meng X . Biomaterials, 2018,162:132. https://www.ncbi.nlm.nih.gov/pubmed/29448141

doi: 10.1016/j.biomaterials.2018.02.022     URL     pmid: 29448141
[24]
Zheng H, Zhang Y, Liu L, Wan W, Guo P, Nyström A M, Zou X . J. Am. Chem. Soc., 2016,138(3):962. https://www.ncbi.nlm.nih.gov/pubmed/26710234

doi: 10.1021/jacs.5b11720     URL     pmid: 26710234
[25]
Dong K, Wang Z, Zhang Y, Ren J, Qu X . ACS Appl. Mater. Interfaces, 2018,10(38):31998.
[26]
Agostinis P, Berg K, Cengel K A, Foster T H, Girotti A W, Gollnick S O, Hahn S M, Hamblin M R, Juzeniene A, Kessel D, Korbelik M, Moan J, Mroz P, Nowis D, Piette J, Wilson B C, Golab J . CA. Cancer J. Clin., 2011,61(4):250. https://www.ncbi.nlm.nih.gov/pubmed/21617154

doi: 10.3322/caac.20114     URL     pmid: 21617154
[27]
Bechet D, Couleaud P, Frochot C, Viriot M L, Guillemin F, Barberi-Heyob M . Trends Biotechnol., 2008,26(11):612. https://www.ncbi.nlm.nih.gov/pubmed/18804298

doi: 10.1016/j.tibtech.2008.07.007     URL     pmid: 18804298
[28]
Lu K, He C, Lin W . J. Am. Chem. Soc., 2015,137(24):7600. https://www.ncbi.nlm.nih.gov/pubmed/26068094

doi: 10.1021/jacs.5b04069     URL     pmid: 26068094
[29]
Sykes E A, Chen J, Zheng G, Chan W C W . ACS Nano, 2014,8(6):5696. https://www.ncbi.nlm.nih.gov/pubmed/24821383

doi: 10.1021/nn500299p     URL     pmid: 24821383
[30]
Park J, Jiang Q, Feng D, Mao L, Zhou H C . J. Am. Chem. Soc., 2016,138(10):3518. https://www.ncbi.nlm.nih.gov/pubmed/26894555

doi: 10.1021/jacs.6b00007     URL     pmid: 26894555
[31]
Allison R R, Sibata C H . Photodiagnosis Photodyn. Ther., 2010,7(2):61. https://www.ncbi.nlm.nih.gov/pubmed/20510301

doi: 10.1016/j.pdpdt.2010.02.001     URL     pmid: 20510301
[32]
Gao S, Zheng P, Li Z, Feng X, Yan W, Chen S, Guo W, Liu D, Yang X, Wang S, Liang X J, Zhang J . Biomaterials, 2018,178:83. https://www.ncbi.nlm.nih.gov/pubmed/29913389

doi: 10.1016/j.biomaterials.2018.06.007     URL     pmid: 29913389
[33]
Cheng H, Zhu J Y, Li S Y, Zeng J Y, Lei Q, Chen K W, Zhang C, Zhang X Z . Adv. Funct. Mater., 2016,26(43):7847.
[34]
Juliano R L . Nucleic Acids Res., 2016,44(14):6518. https://www.ncbi.nlm.nih.gov/pubmed/27084936

doi: 10.1093/nar/gkw236     URL     pmid: 27084936
[35]
Dowdy S F . Nat. Biotechnol., 2017,35(3):222. https://www.ncbi.nlm.nih.gov/pubmed/28244992

doi: 10.1038/nbt.3802     URL     pmid: 28244992
[36]
Panyam J, Labhasetwar V . Adv. Drug Deliv. Rev., 2003,55(3):329. https://www.ncbi.nlm.nih.gov/pubmed/12628320

doi: 10.1016/s0169-409x(02)00228-4     URL     pmid: 12628320
[37]
An J, Geib S J, Rosi N L . J. Am. Chem. Soc., 2009,131(24):8376. https://www.ncbi.nlm.nih.gov/pubmed/19489551

doi: 10.1021/ja902972w     URL     pmid: 19489551
[38]
He C, Lu K, Liu D, Lin W . J. Am. Chem. Soc., 2014,136(14):5181. https://www.ncbi.nlm.nih.gov/pubmed/24669930

doi: 10.1021/ja4098862     URL     pmid: 24669930
[39]
Chen Q, Xu M, Zheng W, Xu T, Deng H, Liu J . ACS Appl. Mater. Interfaces, 2017,9(8):6712. https://pubs.acs.org/doi/10.1021/acsami.6b12792

doi: 10.1021/acsami.6b12792     URL    
[40]
Wang H, Zhang J, Yu H . Free Radic. Biol. Med., 2007,42(10):1524. https://www.ncbi.nlm.nih.gov/pubmed/17448899

doi: 10.1016/j.freeradbiomed.2007.02.013     URL     pmid: 17448899
[41]
Bergamo A, Gaiddon C, Schellens J H M, Beijnen J H, Sava G .J. Inorg. Biochem., 2012,106(1):90.
[42]
Wang S, McGuirk C M, Ross M B, Wang S, Chen P, Xing H, Liu Y, Mirkin C A .J. Am. Chem. Soc., 2017,139(29):9827.
[43]
Morris W, Briley W E, Auyeung E, Cabezas M D, Mirkin C A . J. Am. Chem. Soc., 2014,136(20):7261. https://www.ncbi.nlm.nih.gov/pubmed/24818877

doi: 10.1021/ja503215w     URL     pmid: 24818877
[44]
Peng S, Bie B, Sun Y, Liu M, Cong H, Zhou W, Xia Y, Tang H, Deng H, Zhou X . Nat. Commun., 2018,9(1):1293. https://www.ncbi.nlm.nih.gov/pubmed/29615605

doi: 10.1038/s41467-018-03650-w     URL     pmid: 29615605
[1] 叶淳懿, 杨洋, 邬学贤, 丁萍, 骆静利, 符显珠. 钯铜纳米电催化剂的制备方法及应用[J]. 化学进展, 2022, 34(9): 1896-1910.
[2] 钟琴, 周帅, 王翔美, 仲维, 丁晨迪, 傅佳骏. 介孔二氧化硅基智能递送体系的构建及其在各类疾病治疗中的应用[J]. 化学进展, 2022, 34(3): 696-716.
[3] 李红, 史晓丹, 李洁龄. 肽自组装水凝胶的制备及在生物医学中的应用[J]. 化学进展, 2022, 34(3): 568-579.
[4] 张丹丹, 吴琪, 曲广波, 史建波, 江桂斌. 单细胞水生生物金属纳米颗粒的定量分析[J]. 化学进展, 2022, 34(11): 2331-2339.
[5] 郭玲香, 李菊平, 刘志洋, 李全. 聚集诱导发光型光敏剂用于线粒体靶向光动力治疗[J]. 化学进展, 2022, 34(11): 2489-2502.
[6] 郑明心, 谭臻至, 袁金颖. 光响应Janus粒子体系的构建与应用[J]. 化学进展, 2022, 34(11): 2476-2488.
[7] 荆晓东, 孙莹, 于冰, 申有青, 胡浩, 丛海林. 肿瘤微环境响应药物递送系统的设计[J]. 化学进展, 2021, 33(6): 926-941.
[8] 杨爽, 杨贤鹏, 王宝俊, 王蕾. 基于核酸的纸基荧光生物传感器的设计及应用[J]. 化学进展, 2021, 33(12): 2309-2315.
[9] 刘陈, 李强翔, 张迪, 郦瑜杰, 刘金权, 肖锡林. MCM-41型介孔二氧化硅纳米颗粒的制备及其在DNA生物传感器中的应用[J]. 化学进展, 2021, 33(11): 2085-2102.
[10] 胡安东, 周顺桂, 叶捷. 生物杂化体介导的半人工光合作用:机理、进展及展望[J]. 化学进展, 2021, 33(11): 2103-2115.
[11] 黄炎, 刘国东, 张学记. 新型冠状病毒(COVID-19)的检测和诊断[J]. 化学进展, 2020, 32(9): 1241-1251.
[12] 丁静静, 黄利利, 谢海燕. 基于纳米颗粒的化学发光技术在炎症及肿瘤诊疗中的应用[J]. 化学进展, 2020, 32(9): 1252-1263.
[13] 秦苗, 徐梦洁, 黄棣, 魏延, 孟延锋, 陈维毅. 氧化铁纳米颗粒在磁共振成像中的应用[J]. 化学进展, 2020, 32(9): 1264-1273.
[14] 吴晴, 唐一源, 余淼, 张悦莹, 李杏梅. 基于肿瘤微环境响应的DNA纳米结构递药系统[J]. 化学进展, 2020, 32(7): 927-934.
[15] 薛一凡, 孟文卉, 汪润泽, 任俊杰, 衡伟利, 张建军. 过饱和度理论及过饱和药物递送系统[J]. 化学进展, 2020, 32(6): 698-712.