English
往期目录
新闻公告
More
化学进展 2014, Vol. 26 Issue (06): 1039-1049 DOI: 10.7536/PC131127 前一篇   后一篇

• 综述与评论 •

基于环糊精的靶向药物传递系统

韩彬, 廖霞俐*, 杨波*   

  1. 昆明理工大学生命科学与技术学院 昆明 650500
  • 收稿日期:2013-11-01 修回日期:2014-01-01 出版日期:2014-06-15 发布日期:2014-03-31
  • 通讯作者: 廖霞俐, 杨波 E-mail:xlliao@yahoo.com;yangbo6910@sina.com
  • 基金资助:

    国家自然科学基金项目（No. 21062009，21362016）和云南省应用基础研究项目（No. 2011FZ059）资助

下载PDF ( 2504 ) 引用
导出 被引次数 ( 22 | 2 )

Targeted Drug Delivery Systems Based on Cyclodextrins

Han Bin, Liao Xiali*, Yang Bo*   

  1. Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming 650500, China
  • Received:2013-11-01 Revised:2014-01-01 Online:2014-06-15 Published:2014-03-31
  • Supported by:

    The work was supported by the National Natural Science Foundation of China(No. 21062009, 21362016) and Yunnan Natural Science Foundation Project(No. 2011FZ059)

癌症等恶性增殖疾病的靶向治疗有赖于靶向药物传递系统（targeted drug delivery system，TDDS）的开发。环糊精具有低毒、易修饰等优良性质，并可通过与药物分子形成包合物而提高药物的溶解性、稳定性、安全性和生物利用度等，因而具有成为优秀药物载体的潜力。环糊精不仅可以以其本身或修饰环糊精的形式充当载体，还可通过聚轮烷、阳离子聚合物或纳米粒等形式构建有效的药物载体。肿瘤或人体某些病变部位的细胞表面存在过度表达的生物受体如叶酸受体、去唾液酸糖蛋白受体、透明质酸受体、转铁蛋白受体和整合素受体等，可以与其相应的配体产生特异性识别。用适当的化学方法将配体分子如叶酸、单糖或寡糖、透明质酸、转铁蛋白及RGD肽等键接在基于环糊精的载体上，可形成具有靶向性质的药物载体，进而与药物分子一起构筑靶向药物传递系统。这种药物传递系统不仅针对于化学治疗药物，在核酸传递中也得到了丰富的应用。本文综述了基于环糊精的靶向药物传递系统的靶向机理及最新研究进展，并对其发展前景作了展望。

关键词： 环糊精, 靶向药物传递系统, 受体, 靶向配体

Targeted drug delivery system (TDDS) nowadays has been adopted as a superb approach to the therapies of cancer and other mortal diseases. Cyclodextrins (CDs) are chosen to take the part of a promising drug carrier due to its low toxicity and high flexibility of structure modification. They are commonly used to enhance the aqueous solubility, chemical stability, safety and bioavailability of drugs in virtue of their peculiar ability to form CD/drug inclusion complexes. Not only native and chemically modified cyclodextrins were employed as drug carriers, but also sorts of CD-based more sophisticated carrier systems such as polyrotaxanes/polypseudorotaxanes, polycations and nanoparticles emerged in recent years. Considering the fact that lots of biological receptors such as folate receptor, asialoglycoprotein receptor, hyaluronic receptor, transferrin receptor, integrin receptor are overexpressed on the surface of most cancer cells and other focal cells, design of TDDS containing matching targeting ligands (TLs) could help realize targeted therapy for those focal cells or tissues. Targeting ligands such as folic acid (FA), mono- and oligosaccharides, hyaluronic acid (HA), transferrin, RGD sequence are consequently chemically bound to CD-based carriers to form targeted carrier systems which further furnished TDDS via non-covalent complexation or bio-cleavable conjugation to drug molecules. Such TDDS are also widely applied on nucleic acid delivery in addition to chemotherapeutical drugs. As to depict the important developments, basic targeting principles and the latest progress on targeted drug delivery systems based on CDs are summarized, and also a brief prospect is given in this review.

Contents
1 Introduction
2 Folate receptor-mediated TDDS based on CDs
2.1 Targeting mechanism
2.2 Progress on folate receptor-mediated TDDS based on CDs
3 Asialoglycoprotein receptor-mediated TDDS based on CDs
3.1 Targeting mechanism
3.2 Progress on asialoglycoprotein receptor-mediated TDDS based on CDs
4 Hyaluronic receptor-mediated TDDS based on CDs
4.1 Targeting mechanism
4.2 Progress on hyaluronic receptor-mediated TDDS based on CDs
5 Transferrin receptor-mediated TDDS based on CDs
5.1 Targeting mechanism
5.2 Progress on transferrin receptor-mediated TDDS based on CDs
6 Integrin receptor-mediated TDDS based on CDs
6.1 Targeting mechanism
6.2 Progress on integrin receptor-mediated TDDS based on CDs
7 Other receptor-mediated TDDS based on CDs
8 Conclusion

Key words: cyclodextrin, targeted drug delivery system (TDDS), receptor, targeting ligand

中图分类号: 

()

[1] Yague E, Raguz S. Brit. J. Cancer, 2005, 93: 973.
[2] Tan S Y, Grimes S. Singap. Med. J., 2010, 51: 842.
[3] 闫真芳(Yan Z F), 徐希明(Xu X M), 余江男(Yu J N). 药物生物技术(Pharmaceutical Biotechnology), 2009, 16: 481.
[4] 陈湧(Chen Y), 刘育(Liu Y). 有机化学(Chinese Journal of Organic Chemistry), 2012, 32: 805.
[5] Wang J, Cao Y P, Sun B G, Wang C T. Food Chem., 2011, 127: 1680.
[6] 孙涛(Sun T), 李建业(Li J Y), 郝爱友(Hao A Y). 有机化学(Chinese Journal Organic Chemistry), 2012, 32: 2054.
[7] Loftsson T, Duchene D. Int. J. Pharm., 2007, 329: 1.
[8] Szejtli J. Chem. Rev., 1998, 98: 1743.
[9] Freudenberg K, Cramer F, Plieninger H. DE 895769, 1953.
[10] Chen Y, Liu Y. Chem. Soc. Rev., 2010, 39: 495.
[11] D’Souza V T, Bender M L. Acc. Chem. Res., 1987, 20: 146.
[12] Bilensoy E. Cyclodextrins in Pharmaceutics, Cosmetics, and Biomedicine: Current and Future Industrial Applications. New Jersey: John Wiley, 2011.
[13] Chordiya M A, Senthilkumaran K. J. Pharm. Pharmacol., 2012, 1: 19.
[14] Hwang S J, Bellocq N C, Davis M E. Bioconju. Chem., 2001, 12: 280.
[15] Flourie B, Molis C, Achour L, Dupas H, Hatat C, Rambaud C J. J. Nutr., 1993, 123: 676.
[16] Garcia-Lopez J J, Hemandez-Mateo F, Isac-Garcia L, Kim J M, Roy R, Santoyo-Gonzalez F, Vargas-Berenguel A. J. Org. Chem., 1999, 64: 522.
[17] Hirayama F, Minami K, Uekama K. J. Pharm. Pharmacol., 1996, 48: 27.
[18] Uekama K, Minami K, Hirayama F. J. Med. Chem., 1997, 40: 2755.
[19] El-Kamel A H, Abdel-Aziz A A M, Fatani A J, El-Subbagh H I. Int. J. Pharm., 2008, 358: 248.
[20] Leamon C P, Reddy J A. Adv. Drug. Deliv. Rev., 2004, 56: 1127.
[21] Sabharanjak S, Mayor S. Adv. Drug. Deliv. Rev., 2004, 56: 1099.
[22] Chen C, Ke J Y, Zhou E X, Yi W, Brunzelle J S, Li J, Yong E L, Xu E H, Melcher K. Nature, 2013, 500: 486.
[23] 张莉(Zhang L), 潘俊(Pan J), 陆伟跃(Lu Y W). 国外医药:合成药、生化药、制剂分册(World Pharmacy),2002, 23(6): 359.
[24] Sudimack J, Lee R J. Adv. Drug. Deliv. Rev., 2000, 41: 147.
[25] Leamon C P, Deprince R B, Hendren R W. Drug Target, 1999, 7: 157.
[26] Leamon C P, Cooper S R, Hardee G E. Bioconju. Chem., 2003, 14: 738.
[27] Clementi A, Aversa M C, Corsaro C, Spooren J, Stancanelli R, O’Connor C, McNamara M, Mazzaglia A. J. Incl. Phenom. Macrocycl. Chem., 2011, 69: 321.
[28] Salmaso S, Semenzato A, Caliceti P, Hoebeke J, Sonvico F, Dubernet C, Couvreur P. Bioconju. Chem., 2004, 15: 997.
[29] Yin J J, Sharma S, Shumyak S P, Wang Z X, Zhou Z W, Zhang Y D, Guo P X, Li C Z, Kanwar J R, Yang T X, Mohapatra S S, Liu W Q, Duan W, Wang J C, Li Q, Zhang X J, Tan J, Jia L, Liang J, Wei M Q, Li X T, Zhou S F. PLoS One, 2013, 8: e62289.
[30] Yang Y, Zhang Y M, Chen Y, Zhao D, Chen J T, Liu Y. Chem. Eur. J., 2012, 18: 4208.
[31] 刘育(Liu Y), 杨洋(Yang Y), 张瀛溟(Zhang Y M). CN 102258788B, 2012.
[32] 赖春丽(Lai C L), 赖乐(Lai L), 赵建彬(Zhao J B), 陈建海(Chen J H). 药学学报(Acta Pharmaceutica Sinica), 2010, 45: 920.
[33] Zhou Y, Wang H, Wang C X, Li Y S, Lu W F, Chen S F, Luo J D, Jiang Y N, Chen J H. Mol. Pharm., 2012, 9: 1067.
[34] Zhao F, Yin H, Zhang Z X, Li J. Biomacromolecules, 2013, 14: 476.
[35] Okamatsu A, Motoyama K, Onodera R, Higashi T, Koshigoe T, Shimada Y, Hattori K, Takeuchi T, Arima H. Bioconju. Chem., 2013, 24: 724.
[36] Fallon R J, Schwartz A L. Adv. Drug. Deliv. Rev., 1989, 4: 49.
[37] Donati I, Gamini A, Vetere A, Campa C, Paoletti S. Biomacromolecules, 2002, 3: 805.
[38] Wu J, Nantz M H, Zern M A. Front. Biosci., 2002, 7: d717.
[39] Stockert R J. Physiol. Rev., 1995, 75: 591.
[40] 吴卫(Wu W), 程怡(Cheng Y), 吴琼(Wu Q). 南京医科大学学报(Acta Universitatis Medicinalis Nanjing), 2012, 32:168.
[41] Hattori K, Kenmoku, Mizuguchi T, Ikeda D, Mizuno M, Inazu T. J. Incl. Phenom. Macrocycl. Chem., 2006, 56: 9.
[42] Yasuda N, Aoki N, Abe H, Hattori K. Chem. Lett., 2000, 3: 706.
[43] Pun S H, Bellocq N C, Liu A J, Jensen G, Machemer T, Quijano E, Schluep T, Wen S F, Engler H, Heidel J, Davis M E. Bioconju. Chem., 2004, 15: 831.
[44] 雒琪(Luo Q), 钱皓(Qian H), 王凤山(Wang F S). 中国生化药物杂志(Chinese Journal of Biochemical Pharmaceutics), 2008, 29: 359.
[45] Aruffo A, Stamenkovic I, Melnick M, Underhill C B, Seed B. Cell, 1990, 61: 1303.
[46] Naor D, Sionov R V, Ish-Shalom D. Adv. Cancer Res., 1997, 71: 241.
[47] Naor D, Nedvetzki S, Golan I, Melnik L, Faitelson Y. Crit. Rev. Clin. Lab. Sci., 2002, 39: 527.
[48] Peach R J, Hollenbaygh D, Stamenkovic I, Aruffo A. J. Cell. Biol., 1993, 122: 257.
[49] Oh E J, Park K, Kin K S, Kim J, Yang J A, Kong J H, Lee M Y, Hoffman A S, Hahn S K. J. Control. Release, 2010, 141: 2.
[50] Luo Y, Prestwich G D. Biocunju. Chem., 1999, 10: 755.
[51] Luo Y, Ziebell M R, Prestwich G D. Biomacromolecules, 2000, 1: 208.
[52] Banzato A, Bobisse S, Rondina M, Renier D, Bettella F, Esposito G, Quintieri L, Meléndez-Alafort L, Mazzi U, Zanovello P, Rosato A. Clin. Cancer Res., 2008, 14: 3598.
[53] Galer C E, Sano D S, Ghosh S C, Hah J H, Auzenne E, Hamir A N, Myers J N, Klostergaard J. Oral Oncol., 2011, 47: 1039.
[54] Li J, Huang P, Chang L, Long X, Dong A, Liu J, Chu L, Hu F, Liu J, Deng L. Macromol. Res., 2013, 21, 1331.
[55] Montagner I M, Banzato A, Zuccolotto G, Renier D, Campisi M, Bassi P F, Zanovello P, Rosato A. Urol. Oncol. Semin. Ori., 2013, 31: 1261.
[56] Tsai S W, Yu D S, Tsao S W, Hsu F Y. Int. J. Nanomed., 2012, 8: 2399.
[57] Li S D, Howell S B. Mol. Pharm., 2010, 7: 280.
[58] Tsai S W, Yu D S, Tsao S W, Hsu F Y. Int. J. Nanomed., 2013, 8: 2399.
[59] Dong Z, Zheng W, Xu Z, Yin Z. J. Appl. Polym. Sci., 2013, 130: 927.
[60] Yang X, Dogan I, Pannala V R, Kootala S, Hilborn J, Ossipov D. Polym. Chem., 2013, 4: 4621.
[61] Di Meo D, Panza L, Capitani D, Mannina L, Banzato A, Rondina M, Renier D, Rosato A, Crescenzi V. Biomacromolecules, 2007, 8: 552.
[62] Charlot A, Heyraud A, Guenot P, Rinaudo M, Auzély-Velty R. Biomacromolecules, 2006, 7: 907.
[63] Charlot A, Auzély-Velty R. Macromolecules, 2007, 40: 9555.
[64] Yang Y, Zhang Y M, Chen Y, Chen J T, Liu Y. J. Med. Chem., 2013, 56: 9725.
[65] 刘育(Liu Y), 杨洋(Yang Y), 张瀛溟(Zhang Y M). CN 102698286A, 2012.
[66] 杨媛(Yang Y), 娄琨(Lou K), 梅兴国(Mei X G), 吕万良(Lv W L). 中国药学杂志(Chinese Pharmaceutical Journal), 2009, 44: 1761.
[67] 蒋新国(Jiang X G). 复旦学报(医学版)(Fudan University Journal of Medical Sciences), 2012, 39: 441.
[68] 姜嫣嫣(Jiang Y Y), 裴元英(Pei Y Y). 第六届中国药学会学术年会论文集(Proceeding of the 6th Annual Conference of Chinese Pharmaceutical Association). 北京: 中国药学会(Beijing: Chinese Pharmaceutical Association), 2006. 3797.
[69] Simes S, Slepushkin V, Gaspar R, de Lima M C P, Düzgüne N. Gene Therapy, 1998, 5: 955.
[70] Ishida O, Maruyama K, Tanahashi H, Iwatsuru M, Sasaki K, Eriguchi M, Yanagie H. Pharmaceut. Res., 2001, 18: 1042.
[71] Kursa M, Walker G F, Roesler V, Ogris M, Roedl W, Kircheis R, Wagner E. Bioconju. Chem., 2003, 14: 222.
[72] 叶树楠(Ye S N), 杨述华(Yang S H), 吴强(Wu Q),杨操(Yang C), 李进(Li J), 许伟华(Xu W H). 肿瘤(Tumor), 2005, 25: 321.
[73] Suzuki R, Takizawa T, Kuwata Y, Mutoh M, Ishiguro N, Utoguchi N, Shinohara A, Eriguchi M, Yanagie H, Maruyama K. Int. J. Pharm., 2008, 346: 143.
[74] Hong M, Zhu S, Jiang Y, Tang G, Pei Y. J. Control. Release, 2009, 133: 96.
[75] Hong M, Zhu S, Jiang Y, Tang G, Sun C, Fang C, Shi B, Pei Y. J. Control. Release, 2010, 141: 22.
[76] Nie Y, Schaffert D, Rdl W, Ogris M, Wagner E, Günther M. J. Control. Release, 2011, 152: 127.
[77] Li Y, He H, Jia X, Lu W L, Lou J, Wei Y. Biomaterials, 2012, 33: 3899.
[78] Tros de Ilarduya C, Düezgüene ??塂 N. Expert Opin. Drug Del., 2013, 10: 1583.
[79] Davis M E. Mol. Pharm., 2009, 6: 659.
[80] Heidel J D, Yu Z, Liu J Y, Rele S M, Liang Y, Zeidan R K, Kornbrust D J, Davis M E. Proc. Natl. Acad. Sci. U.S.A., 2007, 104: 5715.
[81] Bartlett D W, Davis M E. Bioconju. Chem., 2007, 18: 456.
[82] Hu-Lieskovan S, Heidel J D, Bartlett D W, Davis M E, Triche T J. Cancer Res., 2005, 65: 8984.
[83] Bellocq N C, Pun S H, Jensen G S, Davis M E. Bioconju. Chem., 2003, 14: 1122.
[84] Pun S H, Tack F, Bellocq N C, Cheng J, Grubbs B H, Jensen G S, Davis M E, Brewster M, Janicot M, Janssens B, Floren W, Bakker A. Canc. Biol. Ther., 2004, 3: 641.
[85] Brahmamdam P, Watanabe E, Unsinger J, Chang K C, Schierding W, Hoekzema A S, Zhou T T, McDonough J S, Holemon H, Heidel J D, Coopersmith C M, McDunn J E, Hotchkiss R S. Shock, 2009, 32: 131.
[86] 安莲效(An L X), 李慧(Li H), 顾月清(Gu Y Q). 中国生化药物杂志(Chinese Journal of Biochemical Pharmaceutics), 2010, 31: 66.
[87] Garanger E, Boturyn D, Dumy P. Anticancer Agents Med. Chem., 2007, 7: 552.
[88] Quan C Y, Chen J X, Wang H Y, Li C, Chang C, Zhang X Z, Zhuo R X. J. Am. Chem. Soc., 2010, 4: 4211.
[89] Tran N Q, Joung Y K, Lih E, Park K M, Park K D. Macromol. Res., 2011, 19: 300.
[90] Miao Q H, Li S P, Han S Y, Wang Z, Wu Y, Nie G J. J. Nanopart. Res., 2012, 14: 1043.
[91] Seo J H, Kakinoki S, Inoue Y, Yamaoka T, Ishihara K, Yui N. J. Am. Chem. Soc., 2013, 135: 5513.
[92] 吴镁春(Wu M C), 王驰(Wang C). 中国新药杂志(Chinese Journal of New Drugs), 2010, 19: 569.
[93] Paliwal S R, Paliwal R, Agarawal G P, Vyas S P. Crit. Rev. Ther. Drug. Carr. Sys., 2012, 29: 421.
[94] Maruta F, Parker A L, Fisher K D, Hallissey M T, Ismail T, Rowlands D C, Chandler L A, Kerr D J, Seymour L W. Cancer Gene Ther., 2002, 9: 543.
[95] Ng K K, Lovell J F, Zheng G. Acc. Chem. Res., 2011, 44: 1105.
[96] Kader A, Pater A. J. Control. Release, 2002, 80: 29.
[97] Shukla J, Sharma U, Kar R, Varma I K, Juyal S, Jagannathan N R, Bandopadhyaya G P. Nanomedicine, 2009, 4: 895.
[98] Hu Y P, Tang G P, Liu J, Cheng W X, Yue Y, Li J C, Zhang P. J. Biomed. Biotechnol., 2012, 989235.
[1] 薛朝鲁门, 刘宛茹, 白图雅, 韩明梅, 莎仁, 詹传郎. 非富勒烯受体DA'D型稠环单元的结构修饰及电池性能研究[J]. 化学进展, 2022, 34(2): 447-459.
[2] 杜宇轩, 江涛, 常美佳, 戎豪杰, 高欢欢, 尚玉. 基于非稠环电子受体的有机太阳能电池材料与器件[J]. 化学进展, 2022, 34(12): 2715-2728.
[3] 任志华, 杨晓溪, 孙振东, 任婧, 桑楠, 周群芳, 江桂斌. 环境内分泌干扰物对雌激素受体表达与转录激活的调控效应及分析技术[J]. 化学进展, 2022, 34(10): 2121-2133.
[4] 侯晓涵, 刘胜男, 高清志. 小分子荧光探针在绿色农药开发中的应用[J]. 化学进展, 2021, 33(6): 1035-1043.
[5] 任飞, 石建兵, 佟斌, 蔡政旭, 董宇平. 具有聚集诱导发光性质的近红外荧光染料[J]. 化学进展, 2021, 33(3): 341-354.
[6] 徐翔, 李坤, 魏擎亚, 袁俊, 邹应萍. 基于非富勒烯小分子受体Y6的有机太阳能电池[J]. 化学进展, 2021, 33(2): 165-178.
[7] 徐云雪, 刘仁发, 徐坤, 戴志飞. 手术导航用荧光探针[J]. 化学进展, 2021, 33(1): 52-65.
[8] 李霞, 马红艳, 聂晓娟, 刘旭, 卞成明, 谢龙. 星形环糊精聚合物的制备及其应用[J]. 化学进展, 2020, 32(7): 935-942.
[9] 沈赵琪, 程敬招, 张小凤, 黄微雅, 温和瑞, 刘诗咏. P3HT/非富勒烯受体异质结有机太阳电池[J]. 化学进展, 2019, 31(9): 1221-1237.
[10] 马明放, 栾天翔, 邢鹏遥, 李兆楼, 初晓晓, 郝爱友. 基于β-环糊精的有机小分子凝胶[J]. 化学进展, 2019, 31(2/3): 225-235.
[11] 朱本占, 沈忱, 盛治国. 膜受体介导双酚A低剂量内分泌干扰效应的分子机制[J]. 化学进展, 2019, 31(1): 167-179.
[12] 赵倩, 李盛华, 刘育*. 环糊精超分子凝胶的构筑及其功能[J]. 化学进展, 2018, 30(5): 673-683.
[13] 卢梦霞, 张涛, 王文, 凌启淡. 基于萘二酰亚胺受体单元的n-型聚合物受体材料在光电领域的研究进展[J]. 化学进展, 2016, 28(6): 872-884.
[14] 姜贺, 靳继彪, 陈润锋, 郑超, 黄维. 基于给-受体结构的热活化延迟荧光材料[J]. 化学进展, 2016, 28(12): 1811-1823.
[15] 谢祥, 吕文珍, 陈润锋, 黄维. 有机太阳能电池给受体材料界面的微纳结构调控[J]. 化学进展, 2016, 28(11): 1591-1600.
阅读次数
全文


摘要

基于环糊精的靶向药物传递系统