English
往期目录
新闻公告
More
化学进展 2011, Vol. 23 Issue (8): 1728-1736 前一篇   后一篇

• 综述与评论 •

叶酸受体介导的肿瘤靶向光学成像技术

费学宁2,1*, 刘丽娟1,2, 朱森2, 刘玉茹2   

  1. 1. 天津大学化工学院 天津 30007;
    2. 天津城市建设学院材料科学与工程系 天津 300384
  • 收稿日期:2010-11-01 修回日期:2010-12-01 出版日期:2011-08-24 发布日期:2011-07-25
  • 通讯作者: 费学宁 E-mail:xueningfei@126.com
  • 基金资助:

    国家自然科学基金项目(No.20772090)和天津市科委重点项目(No.08JCZDJC18200)资助

下载PDF ( 2203 ) 引用
导出 被引次数 ( 14 | 2 )

Targeted Optical Imaging Technology on the Cancer Mediated Folate Receptor

Fei Xuening2,1*, Liu Lijuan1,2, Zhu Sen2, Liu Yuru2   

  1. 1. School of Chemical Engineering and Technology, Tianjin University, Tianjin 30007;
    2. Department of Materials Science and Engineering, Tianjin Institute of Urban Construction, Tianjin 300384, China
  • Received:2010-11-01 Revised:2010-12-01 Online:2011-08-24 Published:2011-07-25

叶酸受体(FR)在肿瘤细胞中都有过度表达,而在正常组织中保守表达,利用叶酸受体与叶酸及其类似物高亲合力结合的特性,将叶酸偶联荧光探针输送到肿瘤组织,从而实现肿瘤组织的特异性靶向光学成像。本文阐述了叶酸荧光探针的结构及其用于标记肿瘤细胞的作用机制,介绍了近十年来叶酸受体介导的肿瘤靶向光学成像技术,例如有机荧光染料,染料掺杂纳米颗粒,量子点,磁性纳米微粒以及多功能纳米粒子等在肿瘤靶向成像中的研究及应用进展,指出了当前研究中的主要发展方向和仍需解决的问题。

关键词： 叶酸受体, 靶向成像, 肿瘤, 荧光染料, 量子点, 染料掺杂纳米颗粒, 多功能纳米粒子

Folate receptor (FR) are up regulated in a broad spectrum of malignant tumors, including cancers of breast, ovary, endometrium, lung, kidney, colon, brain and myeloid cells of hematopoietic origin, while limited expression on normal cells. This over-expression of folate receptors on cancer tissues can be exploited to target folate-linked imaging agents specifically to FR-expressing tumor cells to realize the specific targeted optical imaging by linking folate to fluorescent probes using FR's character of binding folate and folate conjugate with very high affinity . In this review,the schematic of folate fluorescence probe and its mechanism on the marking of tumor cells are introduced. Research and development of FR-mediated tumor targeting optical imaging technology in recent ten years such as the use of organic fluorescent dye, dye-doped nanoparticles, quantum dots (QDs), magnetic nanoparticles and multifunctional particles are summarized. The future prospects and challenges of the current tumor targeted optical imaging research are also proposed in this review. Some FR-mediated tumor targeting optical imaging technologies are shown to be very effective for sensitive cancer imaging with greater success in the cellular level, but most of the experiments are in vitro. There are several challenges in developing fluorescent probes for in vivo cancer imaging applications, such as, to develop NIR fluorescent agents and improve surface modifying technology.

Contents
1 Introduction
2 Structure of composite of folate fluorescent probe
3 Mechanism of tumour cell marked using folate fluorescent probe
4 FR-mediated tumor targeting imaging technology
4.1 Fluorescent dye probe
4.2 Dye-doped nanoparticles
4.3 Quantum dots
4.4 Magnetic nanoparticles
4.5 Multi-functional nanoparticles
5 Potential and challenge of FR-mediated tumor targeting imaging fluorescent probe
6 Expectations

Key words: folate receptor, targeted imaging, cancer, fluorescent dyes, quantum dots, dye-doped nanoparticles, multifunctional nanoparticles

中图分类号: 

()

[1] 卫生部统计信息中心(Statistics information centre of Ministry of Health of the People of Republic of China). 2006年中国卫生事业发展情况统计公报 . http://www.moh.gov.cn/publicfiles/business/htmlfiles/zwgkzt/ptjnj/year2007/p295.htm,http://www.moh.gov.cn/publicfiles/business/htmlfiles/zwgkzt/ptjnj/year2007/p256.htm
[2] Urano Y, Asanuma D, Hama Y, Koyama Y, Barrett T, Kamiya M, Nagano T, Watanabe T, Hasegawa A, Choyke P L, Kobayashi H. Nature Medicine, 2009, 15(1): 104-109
[3] Antony A C. Adv. Drug Deliv. Rev., 2004, 56(8): 1059-1066
[4] Torchilin V P. AAPS Journal, 2007, 9(2): E128-E149
[5] Zhao X B, Lee R J. Adv. Drug Deliv. Rev., 2004, 56(8): 191-193
[6] Reddy J A, Allagadda V M, Leamon C P. Current Pharm. Biotech., 2005, 6(2): 131-150
[7] Zhang B L, Li Y Q, Fang C Y, Chang C C, Chen C S, Chen Y Y, Chang H C. Small, 2009, 5(22): 2716-2721
[8] Sega E I, Low P S. Cancer Metastasis Rev., 2008, 27: 655-664
[9] Toffoli G, Russo A, Gallo A, Cernigoi C, Miotti S, Sorio R, Boiocchi M. Int. J. Cancer, 1998, 79(2): 121-126
[10] Zheng Y, Cai Z, Song X R, Yu B, Bi Y Q, Chen Q H, Zhao D, Xu J P, Hou S X. International Journal of Pharmaceutics, 2009, 382(1/2): 262-269
[11] 费学宁(Fei X N), 刘丽娟(Liu L J), 张宝莲(Zhang B L), 石博杰(Shi B J), 姚康德(Yao K D). 化学进展(Progress in Chemistry), 2006, 18(6): 801-807
[12] 张宝莲(Zhang B L), 石彬(Shi B), 费学宁(Fei X N). 肿瘤防治研究(Cancer Research on Prevention and Treatment), 2010, 37(4): 466-470
[13] Leamon C P, Deprince R B, Hendren R W. Drug Target, 1999, 7(3): 157-169
[14] Leamon C P, Cooper S R, Hardee G E. Bioconjug. Chem., 2003, 14(4): 738-747
[15] Tung C H, Lin Y, Mon W K, Weissleder R. Chem. Biochem., 2002, 3: 784-786
[16] Leamon C P, Reddy J A, Vlahov I R, Vetzel M, Parker N, Nicoson J S, Xu L C, Westrick E. Bioconjug. Chem., 2005, 16(4): 803-811
[17] 雷英杰(Lei Y J), 欧阳杰(Ouyong J), 史小凤(Shi X F). 化学研究与应用(Chem Research and Application), 2008, 20(5): 511-517
[18] Zhou L L, Blessington D, Zhang Z H, Lindenmayer A E, Tung C, Weissleder R, Chance B. Proceedings of the SPIE-The International Society for Optical Engineering, 2003, 4955(1): 505-512
[19] Sakata M, Shirakawa Y, Kamata N, Sakaguchi Y, Nishino H, Ouyang J, Kurosawa K. J. Heterocyclic Chem., 2000, 37: 269-274
[20] Ouyang J, Ouyang C G, Fujii Y, Nakano Y, Shoda T, Nagano T. J. Heterocyclic Chem., 2004, 41(3): 359-365
[21] Moon W K, Lin Y, O' Loughlin T, Tang Y, Kim D E, Weissleder R, Tung C H. Bioconjugate Chem., 2003, 14(3): 539-545
[22] Kennedy M D, Jallad K N, Thompson D H, Amotz D B, Low P S. J. biomed., 2003, 8(4): 636-641
[23] Zheng Y, Cai Z, Song X R, Yu B, Bi Y Q, Chen Q H, Zhao D, Xu J P, Hou S X. International Journal of Pharmaceutics, 2009, 382(1/2): 262-269
[24] 金鑫(Jin X), 张阳德(Zhang Y D), 王吉伟(Wang J W), 张丽华(Zhang L H), 杨璞(Yang P), 张旭(Zhang X), 胡玉(Hu Y), 于丽(Yu L). 中南大学学报(自然科学版) (Journal of Central South University (Science and Technology)), 2010, 41(1): 161-165
[25] Fei X N, Gu Y C, Ban Y, Liu Z J, Zhang B L. Bioorganic & Medicinal Chemistry, 2009, 17(2): 585-591
[26] Fei X N, Yang S B, Zhang B L, Liu Z J, Gu Y C. Journal of Combinatorial Chem., 2007, 9(6): 943-950
[27] Fei X N, Gu Y C, Wang Y Q, Meng Q Y, Zhang B L. Molecules, 2010, 15: 6983-6992
[28] Miki K, Oride K, Inoue S, Kuramochi Y, Nayak R R, Matsuoka H, Harada H, Hiraoka M, Ohe K. Biomaterials, 2010, 31(5): 934-942
[29] Yao G, Wang L, Wu Y R, Smith J, Xu J S, Zhao W J, Lee E, Tan W H. Anal. Bioanal. Chem., 2006, 385(3): 518-524
[30] Zhao X J, Bagwe R P, Tan W H. Adv. Mat., 2004, 16(2): 173-176
[31] Nooney R I, McCahey C M N, Stranik O, Guevel X L, McDonagh C, MacCraith B D. Anal. Bioanal. Chem., 2009, 393(4): 1143-1149
[32] Santra S, Yang H, Dutta D, Stanley J T, Holloway P H, Tan W H, Moudgil B M, Mericle R A. Chem. Commun., 2004, (24): 2810-2811
[33] Santra S, Zhang P, Wang K, Tapec R, Tan W H. Anal. Chem . , 2001, 73(20): 4988-4993
[34] Santra S, Zhang P, Wang K, Tapec R, Tan W H. Journal of Biomedical Optics, 2001, 6(2): 160-166
[35] Qhobosheane M, Santra S, Zhang P, Tan W H. Analyst, 2001, 126: 1274-1278
[36] He X X, Duan J H, Wang K M, Tan W H, Lin X, He C M. Journal of Nanoscience and Nanotechnology, 2004, 4: 585-589
[37] Santra S, Liesenfeld B, Dutta D, Chatel D, Batich C D, Tan W H, Moudgil B M, Mericle R A. Journal of Nanoscience and Nanotechnology, 2005, 5(6): 899-904
[38] Santra S, Dutta D, Moudgil B M. Food and Bioproducts Processing, 2005, 83(2): 136-140
[39] Bailey R E, Nie S. J. Am. Chem. Soc., 2003, 125(23): 7100-7106
[40] Rogach A L, Harrison M T, Kershaw S V, Kornowski A, Burt M G, Eychmüller A, Weller H. Phys. Stat. Sol. (B), 2001, 224(1): 153-158
[41] Zhong X, Han M, Dong Z, White T J, Knoll W. J. Am. Chem. Soc., 2003, 125(28): 8589-8594
[42] Zhong X, Feng Y, Knoll W, Han M Y. J. Am. Chem. Soc., 2003, 125(44): 13559-13563
[43] Pan J, Feng S S. Biomaterials, 2009, 30(6): 1176-1183
[44] 钟丽云(Zhong L Y), 廖问陶(Liao W T), 蔡继业(Cai J Y). 激光生物学报(Acta Laser Biology Sinica), 2007, 16(6): 731-736
[45] Bharali D J, Lucey D W, Jayakumar H, Pudavar H E, Prasad P N. J. Am. Chem. Soc., 2005, 127(32): 11364-11371
[46] Schroeder J E, Shweky I, Shmeeda H, Banin U, Gabizon A. J. Control. Release, 2007, 124(1/2): 28-34
[47] 傅晓源(Fu X Y), 陈富韬(Chen F T), 张浩伟(Zhang H W). 中国现代医学杂志(China Journal of Modern Medicine), 2008, 18(23): 3418-3420
[48] Choi H, Choi S R, Zhou R, Kung H F, Chen I W. Acad. Radiol., 2004, 11(9): 996-1004
[49] Chen T J, Cheng T H, Hung Y C, Lin K T, Liu G C, Wang Y M. Journal of Biomedical Materials Research Part A, 2008, 87A(1): 165-175
[50] Wang S H, Shi X Y, Antwerp M V, Cao Z, Swanson S D, Bi X, Baker J R. Advanced Functional Materials, 2007, 17(16): 3043-3050
[51] Gao J H, Zhang W, Huang P B, Zhang B, Zhang X X, Xu B. J. Am. Chem. Soc., 2008, 130(12): 3710-3711
[52] Zhang Y, Wang S N, Ma S, Guan J J, Li D, Zhang X D, Zhang Z D. J. Biomed. Mater. Res. A, 2008, 85(3): 840-846
[53] Bertorelle F, Wilhelm C, Roger J, Gazeau F, Ménager C, Cabuil V. Langmuir, 2006, 22(12): 5385-5391
[54] Mandal S K, Lequeux N, Rotenberg B, Tramier M, Fattaccioli J, Bibette J, Dubertret B. Langmuir, 2005, 21(9): 4175-4179
[55] Xie H Y, Zuo C, Liu Y, Zhang Z L, Pang D W, Li X L, Gong J P, Dickinson C, Zhou W Z. Small, 2005, 1(5): 506-509
[56] Sun C, Sze R, Zhang M. J. Biomed. Mater. Res. A, 2006, 78(3): 550-557
[57] Wang G P, Song E Q, Xie H Y, Zhang Z L, Tian Z Q, Zuo C, Pang D W, Wu D C, Shi Y B. Chem. Commun., 2005, (34): 4276-4278
[58] Setua S, Menon D, Asok A, Nair S, Koyakutty M. Biomaterials, 2010, 31(4): 714-729
[59] Yan J L, Estevez M C, Smith J E, Wang K M, He X X, Wang L, Tan W H. Nano Today, 2007, 2(3): 44-50
[60] Fei X N, Jia G Z, Wang J, Gu Y C. Acta Physica Polinica A, 2010, 117(6): 333-336
[61] Fei X N, Gu Y C, Wang J, Jia G Z, Liu Z J. Journal of Luminescence, 2011, 131: 291-296
[62] 饶通德(Rao T D). 化工文摘(Chemical Engineering Abstracts), 2009, (2): 59-62
[63] 赵强(Zhao Q), 庞小峰(Pang X F). 原子与分子物理学报(Chinese Journal of Atomic and Molecular Physics), 2005, 22(2): 222-225
[64] 吴伟(Wu W), 贺全国(He Q G), 陈洪(Chen H). 化学进展(Progress in Chemistry), 2008, 20(2/3): 265-272
[65] Guo J, Yang W L, Deng Y H, Wang C C, Fu S K. Small, 2005, 1(7): 737-743
[66] Low P S, Henne W A. Acc. Chem. Res., 2008, 41 (1): 120-129
[67] Reddy J A, Allagadda V M, Leamon C P. Current Pharmaceutical Biotechnology, 2005, 6: 131-150
[1] 顾顺心, 姜琴, 施鹏飞. 发光铱(Ⅲ)配合物抗肿瘤活性研究及应用[J]. 化学进展, 2022, 34(9): 1957-1971.
[2] 冯海弟, 赵璐, 白云峰, 冯锋. 纳米金属有机框架在肿瘤靶向治疗中的应用[J]. 化学进展, 2022, 34(8): 1863-1878.
[3] 陈晓峰, 王开元, 梁芳铭, 姜睿祺, 孙进. 外泌体递药系统及其在肿瘤治疗中的应用[J]. 化学进展, 2022, 34(4): 773-786.
[4] 李程浩, 刘亚敏, 卢彬, 萨拉乌拉, 任先艳, 孙亚平. 碳点的高性能化和功能化改性:方法、特性与展望[J]. 化学进展, 2022, 34(3): 499-518.
[5] 王嘉莉, 朱凌, 王琛, 雷圣宾, 杨延莲. 循环肿瘤细胞及细胞外囊泡的纳米检测技术[J]. 化学进展, 2022, 34(1): 178-197.
[6] 吴星辰, 梁文慧, 蔡称心. 碳量子点的荧光发射机制[J]. 化学进展, 2021, 33(7): 1059-1073.
[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] 许惠凤, 董永强, 朱希, 余丽双. 新型二维材料MXene在生物医学的应用[J]. 化学进展, 2021, 33(5): 752-766.
[9] 刘加伟, 王婧, 王其, 范曲立, 黄维. 激活型有机光声造影剂的应用[J]. 化学进展, 2021, 33(2): 216-231.
[10] 王欣瑜, 赵富平, 张儒, 孙子茹, 刘胜男, 高清志. 抗肿瘤缺氧诱导因子-1的小分子抑制剂[J]. 化学进展, 2021, 33(12): 2259-2269.
[11] 官启潇, 郭和泽, 窦红静. 细胞膜修饰的纳米载体与肿瘤免疫治疗[J]. 化学进展, 2021, 33(10): 1823-1840.
[12] 郭珊, 周翔. 循环肿瘤细胞体内检测技术及其应用研究[J]. 化学进展, 2021, 33(1): 1-12.
[13] 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.
[14] 卫迎迎, 陈琳, 王军丽, 于世平, 刘旭光, 杨永珍. 手性碳量子点的制备及其应用[J]. 化学进展, 2020, 32(4): 381-391.
[15] 孙子茹, 刘胜男, 高清志. 靶向葡萄糖转运蛋白(GLUTs)抗癌药物的开发[J]. 化学进展, 2020, 32(12): 1869-1878.