Please wait a minute...

中国生物工程杂志

CHINA BIOTECHNOLOGY
中国生物工程杂志
中国生物工程杂志  2019, Vol. 39 Issue (6): 48-54    DOI: 10.13523/j.cb.20190607
研究报告     
细胞穿膜肽在肿瘤靶向治疗及疾病诊断中的应用 *
张裕丰,谢梦佳,周舒蕾,徐玲玲,赵铁军()
浙江师范大学化学与生命科学学院 金华 321004
Application of Cell-penetrating Peptides in Tumor Targeted Therapy and Disease Diagnosis
Yu-feng ZHANG,Meng-jia XIE,Shu-lei ZHOU,Ling-ling XU,Tie-jun ZHAO()
College of Chemistry and Life Sciences, Zhejiang Normal University, Jinhua 321004, China
 全文: PDF(490 KB)   HTML
摘要：

近年来细胞穿膜肽(cell-penetrating peptides,CPP)在生物医药领域被广泛应用,它为生物分子的胞内递送提供了有效的策略。关注CPP在肿瘤治疗及疾病诊断中的作用,并重点介绍其在肿瘤靶向治疗和医学影像诊断中的应用及优势。同时,根据CPP在药物传递系统中的特点,改进CPP存在的不足,扩大其联合用药的可能性,这也成为CPP研究的热点。对CPP及其在肿瘤等疾病的诊断及治疗中的应用作一综述,并简述其优化及改进策略,以期促进CPP在临床中的应用。
关键词： 穿膜肽;  肿瘤;  CPP    
Abstract:

In recent years, cell-penetrating peptides (CPP) have provided an effective strategy for intracellular delivery of biomolecules in the biomedical field. The application of CPP in cancer treatment and disease diagnosis were focused, mainly focused on its roles and advantages in tumor targeted therapy and medical imaging diagnosis. Meanwhile, according to the characteristics of CPP in drug delivery system, the deficiency of CPP should be improved to expand the possibility of combined drug utility, which has become the research hotspot.CPP and its applications were reviewed, then describes some optimized and improved methods to expand the clinical application of CPP.
Key words: Target peptides    Cancer    CPP
收稿日期: 2018-11-07 出版日期: 2019-07-12
ZTFLH:  Q816  
基金资助: * 国家自然科学基金(31470262);浙江省公益性技术应用研究计划资助项目(2015C33149)
通讯作者: 赵铁军     E-mail: tjzhao@zjnu.cn
服务　　
把本文推荐给朋友
加入引用管理器
E-mail Alert
RSS
作者相关文章　　
张裕丰
谢梦佳
周舒蕾
徐玲玲
赵铁军

引用本文:

张裕丰,谢梦佳,周舒蕾,徐玲玲,赵铁军. 细胞穿膜肽在肿瘤靶向治疗及疾病诊断中的应用 *[J]. 中国生物工程杂志, 2019, 39(6): 48-54.

Yu-feng ZHANG,Meng-jia XIE,Shu-lei ZHOU,Ling-ling XU,Tie-jun ZHAO. Application of Cell-penetrating Peptides in Tumor Targeted Therapy and Disease Diagnosis. China Biotechnology, 2019, 39(6): 48-54.

链接本文:

https://manu60.magtech.com.cn/biotech/CN/10.13523/j.cb.20190607    或    https://manu60.magtech.com.cn/biotech/CN/Y2019/V39/I6/48

CPP Amino acid sequence
Polyariginines RRRRRRRRR(R9)
Tat49-57 RKKRRQRRR
Penetratin(Antennapedia) RQIKIWFQNRRMKWKK
Pep-1 KETWWETWWTEWSQPKKKRKV
表1  常用细胞穿膜肽
[1] Heitz F, Morris M C, Divita G . Twenty years of cell-penetrating peptides: from molecular mechanisms to therapeutics. British Journal of Pharmacology, 2009,157(2):195-206.
doi: 10.1111/j.1476-5381.2009.00057.x
[2] Guidotti G, Brambilla L, Rossi D . Cell-penetrating peptides: from basic research to clinics. Trends in Pharmacological Sciences, 2017,38(4):406-424.
doi: 10.1016/j.tips.2017.01.003
[3] Frankel A D, Pabo C O . Cellular uptake of the tat protein from human immunodeficiency virus. Cell, 1988,55(6):1189-1193.
doi: 10.1016/0092-8674(88)90263-2
[4] Green M, Loewenstein P M . Autonomous functional domains of chemically synthesized human immunodeficiency virus tat trans-activator protein. Cell, 1988,55(6):1179-1188.
doi: 10.1016/0092-8674(88)90262-0
[5] Ruben S, Perkins A, Purcell R , et al. Structural and functional characterization of human immunodeficiency virus tat protein. Journal of Virology, 1989,63(1):1-8.
[6] Park J, Ryu J, Kim K A , et al. Mutational analysis of a human immunodeficiency virus type 1 Tat protein transduction domain which is required for delivery of an exogenous protein into mammalian cells. The Journal of general virology, 2002,83(Pt 5):1173-1181.
doi: 10.1099/0022-1317-83-5-1173
[7] Joliot A, Pernelle C, Deagostini-Bazin H , et al. Antennapedia homeobox peptide regulates neural morphogenesis. Proceedings of the National Academy of Sciences of the United States of America, 1991,88(5):1864-1868.
doi: 10.1073/pnas.88.5.1864
[8] Derossi D, Joliot A H, Chassaing G , et al. The third helix of the Antennapedia homeodomain translocates through biological membranes. The Journal of Biological Chemistry, 1994,269(14):10444-10450.
[9] Vasconcelos L, Parn K, Langel U . Therapeutic potential of cell-penetrating peptides. Therapeutic Delivery, 2013,4(5):573-591.
doi: 10.4155/tde.13.22
[10] Martin M E, Rice K G . Peptide-guided gene delivery. The AAPS Journal, 2007,9(1):E18-29.
doi: 10.1208/aapsj0901003
[11] El-Sayde A, Futaki S, Harashima H . Delivery of macromolecules using arginine-rich cell-penetrating peptides: ways to overcome endosomal entrapment. The AAPS Journal, 2009,11(1):13-22.
[12] Regberg J, Srimanee A, Langel U . Applications of cell-penetrating peptides for tumor targeting and future cancer therapies. Pharmaceuticals, 2012,5(9):991-1007.
doi: 10.3390/ph5090991
[13] Dokka S, Toledo-Velasquez D, Shi X , et al. Cellular delivery of oligonucleotides by synthetic import peptide carrier. Pharmaceutical Research, 1997,14(12):1759-1764.
doi: 10.1023/A:1012188014919
[14] Nakayama F, Yasuda T, Umeda S , et al. Fibroblast growth factor-12 (FGF12) translocation into intestinal epithelial cells is dependent on a novel cell-penetrating peptide domain: involvement of internalization in the in vivo role of exogenous FGF12. The Journal of Biological Chemistry, 2011,286(29):25823-25834.
doi: 10.1074/jbc.M110.198267
[15] Fernandez-Carneado J, Kogan M J, Pujals S , et al. Amphipathic peptides and drug delivery. Biopolymers, 2004,76(2):196-203.
doi: 10.1002/bip.v76:2
[16] Tian H, Lin L, Chen J , et al. RGD targeting hyaluronic acid coating system for PEI-PBLG polycation gene carriers. Journal of Controlled Release, 2011,155(1):47-53.
doi: 10.1016/j.jconrel.2011.01.025
[17] Elliott G, O’Hare P . Intercellular trafficking of VP22-GFP fusion proteins. Gene Therapy, 1999,6(1):149-151.
[18] Dietrich U, Durr R, Koch J . Peptides as drugs: from screening to application. Current Pharmaceutical Biotechnology, 2013,14(5):501-512.
doi: 10.2174/13892010113149990205
[19] Morris M C, Deshayes S, Heitz F , et al. Cell-penetrating peptides: from molecular mechanisms to therapeutics. Biology of the Cell, 2008,100(4):201-217.
doi: 10.1042/BC20070116
[20] Fonseca S B, Pereira M P, Kelley S O . Recent advances in the use of cell-penetrating peptides for medical and biological applications. Advanced Drug Delivery Reviews, 2009,61(11):953-964.
doi: 10.1016/j.addr.2009.06.001
[21] Richard J P, Melikov K, Vives E , et al. Cell-penetrating peptides. A reevaluation of the mechanism of cellular uptake. The Journal of Biological Chemistry, 2003,278(1):585-590.
doi: 10.1074/jbc.M209548200
[22] Futaki S, Nakase I, Tadokoro A , et al. Arginine-rich peptides and their internalization mechanisms. Biochemical Society Transactions, 2007,35(Pt 4):784-787.
doi: 10.1042/BST0350784
[23] Mayor S, Pagano R E . Pathways of clathrin-independent endocytosis. Nature Reviews Molecular Cell Biology, 2007,8(8):603-612.
[24] Maler L . Solution NMR studies of cell-penetrating peptides in model membrane systems. Advanced Drug Delivery Reviews, 2013,65(8):1002-1011.
doi: 10.1016/j.addr.2012.10.011
[25] Prochiantz A . Homeoprotein intercellular transfer, the hidden face of cell-penetrating peptides. Methods in Molecular Biology, 2011,683(683):249.
doi: 10.1007/978-1-60761-919-2
[26] Mor A, Nguyen V H, Delfour A , et al. Isolation, amino acid sequence, and synthesis of dermaseptin, a novel antimicrobial peptide of amphibian skin. Biochemistry, 1991,30(36):8824-8830.
doi: 10.1021/bi00100a014
[27] Shai Y . Mode of action of membrane active antimicrobial peptides. Biopolymers, 2002,66(4):236-248.
doi: 10.1002/(ISSN)1097-0282
[28] Farkhani S M, Valizadeh A, Karami H , et al. Cell penetrating peptides: efficient vectors for delivery of nanoparticles, nanocarriers, therapeutic and diagnostic molecules. Peptides, 2014,57(7):78-94.
doi: 10.1016/j.peptides.2014.04.015
[29] Ruoslahti E . Tumor penetrating peptides for improved drug delivery. Advanced Drug Delivery Reviews, 2017, 110-111:3-12.
doi: 10.1016/j.addr.2016.03.008
[30] Deshayes S, Morris M, Heitz F , et al. Delivery of proteins and nucleic acids using a non-covalent peptide-based strategy. Advanced Drug Delivery Reviews, 2008,60(4-5):537-547.
doi: 10.1016/j.addr.2007.09.005
[31] Rothbard J B, Garlington S, Lin Q , et al. Conjugation of arginine oligomers to cyclosporin A facilitates topical delivery and inhibition of inflammation. Nature Medicine, 2000,6(11):1253-1257.
[32] Lindgren M, Rosenthal-Aizman K, Saar K , et al. Overcoming methotrexate resistance in breast cancer tumour cells by the use of a new cell-penetrating peptide. Biochemical Pharmacology, 2006,71(4):416-425.
doi: 10.1016/j.bcp.2005.10.048
[33] Mccusker C T, Wang Y, Shan J , et al. Inhibition of experimental allergic airways disease by local application of a cell-penetrating dominant-negative STAT-6 peptide. Journal of Immunology, 2007,179(4):2556-2564.
doi: 10.4049/jimmunol.179.4.2556
[34] Tamura K, Arakawa H, Suzuki M , et al. Novel dinucleotide repeat polymorphism in the first exon of the STAT-6 gene is associated with allergic diseases. Clinical and Experimental Allergy, 2001,31(10):1509-1514.
doi: 10.1046/j.1365-2222.2001.01191.x
[35] Hotchkiss R S, Swanson P E, Freeman B D , et al. Apoptotic cell death in patients with sepsis, shock, and multiple organ dysfunction. Critical Care Medicine, 1999,27(7):1230-1251.
doi: 10.1097/00003246-199907000-00002
[36] Hotchkiss R S, Tinsley K W, Swanson P E , et al. Depletion of dendritic cells, but not macrophages, in patients with sepsis. Journal of Immunology, 2002,168(5):2493-2500.
doi: 10.4049/jimmunol.168.5.2493
[37] Hotchkiss R S, Swanson P E, Knudson C M , et al. Overexpression of Bcl-2 in transgenic mice decreases apoptosis and improves survival in sepsis. Journal of Immunology, 1999,162(7):4148-4156.
[38] Hotchkiss R S, Mcconnell K W, Bullok K , et al. TAT-BH4 and TAT-Bcl-xL peptides protect against sepsis-induced lymphocyte apoptosis in vivo. Journal of Immunology, 2006,176(9):5471-5477.
doi: 10.4049/jimmunol.176.9.5471
[39] Patil S D, Rhodes D G, Burgess D J . DNA-based therapeutics and DNA delivery systems: a comprehensive review. The AAPS Journal, 2005,7(1):E61-77.
[40] Akhtar S, Juliano R L . Cellular uptake and intracellular fate of antisense oligonucleotides. Trends in Cell Biology, 1992,2(5):139-144.
doi: 10.1016/0962-8924(92)90100-2
[41] Lo S L, Wang S . An endosomolytic Tat peptide produced by incorporation of histidine and cysteine residues as a nonviral vector for DNA transfection. Biomaterials, 2008,29(15):2408-2414.
doi: 10.1016/j.biomaterials.2008.01.031
[42] Ray A, Norden B . Peptide nucleic acid (PNA): its medical and biotechnical applications and promise for the future. FASEB J, 2000,14(9):1041-1060.
doi: 10.1096/fasebj.14.9.1041
[43] Mcmanus M T, Sharp P A . Gene silencing in mammals by small interfering RNAs. Nature Reviews Genetics, 2002,3(10):737-747.
[44] Chiu Y L, Alia A, Chu C Y , et al. Visualizing a correlation between siRNA localization, cellular uptake, and RNAi in living cells. Chemistry & Biology, 2004,11(8):1165-1175.
[45] Johnson L N, Cashman S M, Kumar-Singh R . Cell-penetrating peptide for enhanced delivery of nucleic acids and drugs to ocular tissues including retina and cornea. Molecular Therapy, 2008,16(1):107-114.
doi: 10.1038/sj.mt.6300324
[46] Rozenzhak S M, Kadakia M P, Caserta T M , et al. Cellular internalization and targeting of semiconductor quantum dots. Chemical Communications, 2005,17(17):2217-2219.
[47] Santra S, Yang H, Dutta D , et al. TAT conjugated, FITC doped silica nanoparticles for bioimaging applications. Chemical Communications, 2004,24(24):2810-2811.
[48] Webster A, Compton S J, Aylott J W . Optical calcium sensors: development of a generic method for their introduction to the cell using conjugated cell penetrating peptides. The Analyst, 2005,130(2):163-170.
doi: 10.1039/b413725f
[49] Jiang T, Olson E S, Nguyen Q T , et al. Tumor imaging by means of proteolytic activation of cell-penetrating peptides. Proceedings of the National Academy of Sciences of the United States of America, 2004,101(51):17867-17872.
doi: 10.1073/pnas.0408191101
[50] Alivisatos A P, Johnsson K P, Peng X , et al. Organization of ‘nanocrystal molecules’ using DNA. Nature, 1996,382(6592):609-611.
[51] Ballou B, Lagerholm B C, Ernst L A , et al. Noninvasive imaging of quantum dots in mice. Bioconjugate Chemistry, 2004,15(1):79-86.
doi: 10.1021/bc034153y
[52] Silver J, Ou W . Photoactivation of quantum dot fluorescence following endocytosis. Nano Letters, 2005,5(7):1445-1449.
doi: 10.1021/nl050808n
[53] Lagerholm B C, Weinreb G E, Jacobson K , et al. Detecting microdomains in intact cell membranes. Annual Review of Physical Chemistry, 2005,56(1):309-336.
doi: 10.1146/annurev.physchem.56.092503.141211
[54] Delehanty J B, Medintz I L, Pons T , et al. Self-assembled quantum dot-peptide bioconjugates for selective intracellular delivery. Bioconjugate Chemistry, 2006,17(4):920-927.
doi: 10.1021/bc060044i
[55] Yu W, Zhan Y, Xue B , et al. Highly efficient cellular uptake of a cell-penetrating peptide (CPP) derived from the capsid protein of porcine circovirus type 2. Journal of Biological Chemistry, 2018,293(3):15221-15232.
doi: 10.1074/jbc.RA118.004823
[56] Ruoslahti E, Bhatia S N, Sailor M J . Targeting of drugs and nanoparticles to tumors. Journal of Cell Biology, 2010,188(6):759-768.
doi: 10.1083/jcb.200910104
[57] Tan M, Lan K H, Yao J , et al. Selective inhibition of ErbB2-overexpressing breast cancer in vivo by a novel TAT-based ErbB2-targeting signal transducers and activators of transcription 3-blocking peptide. Cancer Research, 2006,66(7):3764-3772.
doi: 10.1158/0008-5472.CAN-05-2747
[58] Salazar M D, Ratnam M . The folate receptor: what does it promise in tissue-targeted therapeutics. Cancer Metastasis Reviews, 2007,26(1):141-152.
doi: 10.1007/s10555-007-9048-0
[59] Kunath K, Merdan T, Hegener O , et al. Integrin targeting using RGD-PEI conjugates for in vitro gene transfer. The Journal of Gene Medicine, 2003,5(7):588-599.
doi: 10.1002/jgm.382
[60] Wang L, Su W, Liu Z , et al. CD44 antibody-targeted liposomal nanoparticles for molecular imaging and therapy of hepatocellular carcinoma. Biomaterials, 2012,33(20):5107-5114.
doi: 10.1016/j.biomaterials.2012.03.067
[61] Xu Y, Wang B, Kaur R , et al. A Supramolecular [10] CPP junction enables efficient electron transfer in modular porphyrin-[10] CPP supersetFullerene complexes. Angewandte Chemie, 2018,57(36):11549-11553.
doi: 10.1002/anie.201802443
[62] Bolton S J, Jones D N, Darker J G , et al. Cellular uptake and spread of the cell-permeable peptide penetratin in adult rat brain. The European Journal of Neuroscience, 2000,12(8):2847-2855.
doi: 10.1046/j.1460-9568.2000.00171.x
[63] Lim K J, Sung B H, Shin J R , et al. A cancer specific cell-penetrating peptide, BR2, for the efficient delivery of an scFv into cancer cells. PLoS One, 2013,8(6):e66084.
doi: 10.1371/journal.pone.0066084
[64] Leriche G, Chisholm L, Wanger A . Cleavable linkers in chemical biology. Bioorganic & Medicinal Chemistry, 2012,20(2):571-582.
[65] Alves I D, Carre M, Montero M P , et al. A proapoptotic peptide conjugated to penetratin selectively inhibits tumor cell growth. Biochimica et Biophysica Acta, 2014,1838(8):2087-2098.
doi: 10.1016/j.bbamem.2014.04.025
[66] Choi K Y, Swierczewska M, Lee S , et al. Protease-activated drug development. Theranostics, 2012,2(2):156-178.
doi: 10.7150/thno.4068
[67] Orzechowska E J, Kozlowska E, Czubaty A , et al. Controlled delivery of BID protein fused with TAT peptide sensitizes cancer cells to apoptosis. BMC Cancer, 2014,14(1):771.
doi: 10.1186/1471-2407-14-771
[68] Wang H X, Yang X Z, Sun C Y , et al. Matrix metalloproteinase 2-responsive micelle for siRNA delivery. Biomaterials, 2014,35(26):7622-7634.
doi: 10.1016/j.biomaterials.2014.05.050
[69] Chang X, Hou Y . Expression of RecA and cell-penetrating peptide (CPP) fusion protein in bacteria and in mammalian cells. International Journal of Biochemistry and Molecular Biology, 2018,9(1):1-10.
[1] 赵梦泽,李凤智,王鹏银,李剑,徐寒梅. PD-L1和VEGF双靶点联合阻断治疗的研究进展[J]. 中国生物工程杂志, 2021, 41(9): 71-77.
[2] 吕慧中,赵晨辰,朱链,许娜. 外泌体靶向递药在肿瘤治疗中的进展[J]. 中国生物工程杂志, 2021, 41(5): 79-86.
[3] 原博,王杰文,康广博,黄鹤. 双特异性纳米抗体的研究进展及其应用 *[J]. 中国生物工程杂志, 2021, 41(2/3): 78-88.
[4] 邓蕊,曾佳利,卢雪梅. 基于Musca domestica cecropin的抗肿瘤小分子衍生肽筛选及构效关系解析*[J]. 中国生物工程杂志, 2021, 41(11): 14-22.
[5] 蔺士新,刘东晨,雷云,熊盛,谢秋玲. TNF-α纳米抗体的筛选、表达及特异性检测 *[J]. 中国生物工程杂志, 2020, 40(7): 15-21.
[6] 杨威,宋方祥,王帅,张黎,王红霞,李焱. 药物输送系统中Janus纳米粒子的制备及应用 *[J]. 中国生物工程杂志, 2020, 40(7): 70-81.
[7] 张保惠,熊华龙,张天英,袁权. 基于水疱性口炎病毒(VSV)的溶瘤病毒研究进展 *[J]. 中国生物工程杂志, 2020, 40(6): 53-62.
[8] 童梅,程永庆,刘金毅,徐晨. 促进大肠杆菌周质空间小分子抗体表达的菌种构建方法*[J]. 中国生物工程杂志, 2020, 40(5): 48-56.
[9] 戴奇男,张景红. 肿瘤多药耐药与自噬、DNA修复和肿瘤干细胞相关的分子机制研究进展 *[J]. 中国生物工程杂志, 2020, 40(4): 69-77.
[10] 钱颖,钱晨,白晓庆,王晶晶. 免疫佐剂在肿瘤免疫疗法中的应用进展 *[J]. 中国生物工程杂志, 2020, 40(3): 96-103.
[11] 肖雪筠,唐奇,新华·那比. 靶向肿瘤微环境的CAR-T治疗研究*[J]. 中国生物工程杂志, 2020, 40(12): 67-74.
[12] 何询,张鹏,张俊祥. 类器官的构建与应用进展[J]. 中国生物工程杂志, 2020, 40(12): 82-87.
[13] 朱永朝,陶金,任萌萌,熊燃,何亚琴,周瑜,卢震辉,杜勇,杨芝红. 自噬抑制肿瘤坏死因子α诱导人胎盘胎儿来源间充质干细胞发生凋亡 *[J]. 中国生物工程杂志, 2019, 39(9): 62-67.
[14] 彭贤贵,杨武晨,李佳,苟阳,王平,刘思恒,张云,李艺,张曦. 细胞形态相关技术在血液系统肿瘤中的应用 *[J]. 中国生物工程杂志, 2019, 39(9): 84-90.
[15] 刘艳,戴鹏,朱运峰. 外泌体作为肿瘤标志物的研究进展 *[J]. 中国生物工程杂志, 2019, 39(8): 74-79.
主管：中国科学院 　主办：中国科学院文献情报中心 　中国生物技术发展中心 　中国生物工程学会