RGD 肽介导的脑胶质瘤靶向治疗和显像的研究进展

陈中亚,赵 雁,陶 涛*

主办:上海医药工业研究院
   中国药学会
   中国化学制药工业协会
ISSN 1001-8255   CN 31-1243/R   ZYGZEA
中国医药工业杂志 ›› 2013, Vol. 44 ›› Issue (3) : 290-295.
综述与专论 Review

RGD 肽介导的脑胶质瘤靶向治疗和显像的研究进展

作者信息 +

Progress in RGD Peptide-mediated Targeted Therapy and Imaging for Glioma

Author information +
History +

摘要

RGD 肽是含有精氨酸- 甘氨酸- 门冬氨酸(Arg-Gly-Asp) 序列的一类短肽,能和细胞表面的整合素受体特异性结合。整合素受体,尤其是αvβ3 高表达于脑胶质瘤等肿瘤细胞表面,而在成熟血管内皮细胞呈低表达。因此,在脑胶质瘤的靶向治疗和显像研究中外源性RGD 肽与肿瘤细胞表面的整合素受体的竞争性结合得到广泛研究。本文综述了RGD 肽介导的脑胶质瘤靶向治疗及显像的典型方法及近年来的研究进展。

Abstract

RGD peptides are small peptides containing arginine-glycine-aspartic acid triple peptide motif and can bind specifically to integrin receptors on cell surface. Integrin receptors, especially αvβ3, are highly expressed on tumor cell (glioma for example) surface while showing low expression on mature endothelial cells. Therefore, in the studies of targeted therapy and imaging for glioma, the competitive binding between ectogenic RGD peptides and integrin receptors on the tumor cell surface has been widely studied. In this paper, the typical methods and progress in RGD peptide-mediated targeted therapy and imaging for glioma in recent years are reviewed.

关键词

RGD 肽 / 脑胶质瘤 / 整合素 / 靶向治疗 / 显像 / 综述

Key words

RGD peptide / glioma / integrin / targeted therapy / imaging / review

引用本文

导出引用
陈中亚,赵 雁,陶 涛*. RGD 肽介导的脑胶质瘤靶向治疗和显像的研究进展. 中国医药工业杂志. 2013, 44(3): 290-295
CHEN Zhongya, ZHAO Yan, TAO Tao*. Progress in RGD Peptide-mediated Targeted Therapy and Imaging for Glioma. Chinese Journal of Pharmaceuticals. 2013, 44(3): 290-295

参考文献

[1] Zitzmann S, Ehemann V, Schwab M. Arginine-glycineaspartic acid (RGD)-peptide binds to both tumor and tumorendothelial

cells in vivo [J]. Cancer Res, 2002, 62(18): 5139-5143.

[2] Liu Y, Lu W. Recent advances in brain tumor-targeted nanodrug delivery systems [J]. Expert Opin Drug Deliv, 2012, 9(6): 671-686.

[3] Zhan C, Lu W. The blood-brain/tumor barriers: challenges and chances for malignant gliomas targeted drug delivery [J]. Curr Pharm Biotechnol, 2012, 13(12): 2380-2387.

[4] Nabors LB, Mikkelsen T, Rosenfeld SS, et al. Phase I and correlative biology study of cilengitide in patients with recurrent malignant glioma [J]. J Clin Oncol, 2007, 25(13): 1651-1657.

[5] Reardon D, Fink K, Nabors B, et al. Phase IIa trial of cilengitide (EMD121974) single-agent therapy in patients (pts) with recurrent glioblastoma (GBM): EMD 121974-009 [J]. J Clin Oncol, 2007, 25(18 Suppl): 2002-2012.

[6] Friess H, Langrehr JM, Oettle H, et al. A randomized multicenter phase II trial of the angiogenesis inhibitor Cilengitide (EMD 121974) and gemcitabine compared with gemcitabine alone in advanced unresectable pancreatic cancer [J]. BMC Cancer, 2006, 6(1): 285-296.

[7] Curnis F, Gasparri A, Sacchi A, et al. Coupling tumor necrosis factor-alpha with alphaV integrin ligands improves its antineoplastic activity [J]. Cancer Res, 2004, 64(2): 565-571.

[8] Suh W, Han SO, Yu L, et al. An angiogenic, endothelial-celltargeted polymeric gene carrier [J]. Mol Ther, 2002, 6(5): 664-672.

[9] Miller CR, Buchsbaum DJ, Reynolds PN, et al. Differential susceptibility of primary and established human glioma cells to adenovirus infection: targeting via the epidermal growth factor receptor achieves fiber receptor-independent gene transfer [J]. Cancer Res, 1998, 58(24): 5738-5748.

[10] Reynolds P, Dmitriev I, Curiel D. Insertion of an RGD motif into the HI loop of adenovirus fiber protein alters the distribution of transgene expression of the systemically administered vector [J]. Gene Ther, 1999, 6(7): 1336-1339.

[11] Fueyo J, Alemany R, Gomez-Manzano C, et al. Preclinical characterization of the antiglioma activity of a tropismenhanced adenovirus targeted to the retinoblastoma pathway [J]. J Natl Cancer Inst, 2003, 95(9): 652-660.

[12] Yong RL, Shinojima N, Fueyo J, et al. Human bone marrowderived mesenchymal stem cells for intravascular delivery of oncolytic adenovirus Delta24-RGD to human gliomas [J]. Cancer Res, 2009, 69(23): 8932-8940.

[13] Zhang L, Zhu S, Qian L, et al. RGD-modified PEGPAMAM-DOX conjugates: in vitro and in vivo studies for glioma [J]. Eur J Pharm Biopharm, 2011, 79(2): 232-240.

[14] Waite CL, Roth CM. PAMAM-RGD conjugates enhance siRNA delivery through a multicellular spheroid model of malignant glioma [J] . Bioconjug Chem, 2009, 20(10) : 1908-1916.

[15] Liu X, Cui W, Li B, et al. Targeted therapy for glioma using cyclic RGD-entrapped polyionic complex nanomicelles [J]. Int J Nanomedicine, 2012, 7: 2853-2862.

[16] Chen Z, Deng J, Zhao Y, et al. Cyclic RGD peptide-modified liposomal drug delivery system: enhanced cellular uptake in vitro and improved pharmacokinetics in rats [J]. Int J Nanomedicine, 2012, 7: 3803-3811.

[17] Liu Z, Shi J, Jia B, et al. Two 90Y-labeled multimeric RGD peptides RGD4 and 3PRGD2 for integrin targeted radionuclide therapy [J]. Mol Pharm, 2011, 8(2): 591-599.

[18] Gross S, Piwnica-Worms D. Spying on cancer: molecular imaging in vivo with genetically encoded reporters [J]. Cancer Cell, 2005, 7(1): 5-15.

[19] Chen X, Park R, Shahinian AH, et al. 18F-labeled RGD peptide: initial evaluation for imaging brain tumor angiogenesis [J]. Nucl Med Biol, 2004, 31(2): 179-189.

[20] Chen X, Park R, Hou Y, et al. MicroPET imaging of brain tumor angiogenesis with 18F-labeled PEGylated RGD peptide [J]. Eur J Nucl Med Mol Imaging, 2004, 31(8): 1081-1089.

[21] Wu Z, Li ZB, Cai W, et al. 18F-labeled mini-PEG spacered RGD dimer ( 18F-FPRGD2) : synthesis and microPET imaging of αvβ3 integrin expression [J]. Eur J Nucl Med Mol Imaging, 2007, 34(11): 1823-1831.

[22] Schnell O, Krebs B, Carlsen J, et al. Imaging of integrin αvβ3 expression in patients with malignant glioma by [18F] Galacto-RGD positron emission tomography [J]. Neuro Oncol, 2009, 11(6): 861-870.

[23] Wu Z, Li ZB, Chen K, et al. MicroPET of tumor integrin αvβ3 expression using 18F-labeled PEGylated tetrameric RGD peptide (18F-FPRGD4) [J]. J Nucl Med, 2007, 48(9): 1536-1544.

[24] Wu Y, Zhang X, Xiong Z, et al. MicroPET imaging of glioma integrin αvβ3 expression using 64Cu-labeled tetrameric RGD peptide [J]. J Nucl Med, 2005, 46(10): 1707-1718.

[25] Li ZB, Cai W, Cao Q, et al. 64Cu-labeled tetrameric and octameric RGD peptides for small-animal PET of tumor αvβ3 integrin expression [J]. J Nucl Med, 2007, 48(7): 1162-1171.

[26] Shi J, Kim YS, Zhai S, et al. Improving tumor uptake and pharmacokinetics of 64Cu-labeled cyclic RGD peptide dimers with Gly(3) and PEG(4) linkers [J]. Bioconjug Chem, 2009, 20(4): 750-759.

[27] Liu Z, Cai W, He L, et al. In vivo biodistribution and highly efficient tumour targeting of carbon nanotubes in mice [J]. Nat Nanotechnol, 2006, 2(1): 47-52.

[28] Li ZB, Chen K, Chen X. 68Ga-labeled multimeric RGD peptides for microPET imaging of integrin αvβ3 expression [J]. Eur J Nucl Med Mol Imaging, 2008, 35(6): 1100-1108.

[29] Morales-Avila E, Ferro-Flores G, Ocampo-García BE, et al. Multimeric system of 99mTc-labeled gold nanoparticles conjugated to c[RGDfK(C) ] for molecular imaging of tumor αvβ3 expression [J]. Bioconjug Chem, 2011, 22(5): 913-922.

[30] Chen X, Conti PS, Moats RA. In vivo near-infrared fluorescence imaging of integrin αvβ3 in brain tumor xenografts [J]. Cancer Res, 2004, 64(21): 8009-8014.

[31] Hsu AR, Hou LC, Veeravagu A, et al. In vivo near-infrared fluorescence imaging of integrin αvβ3 in an orthotopic glioblastoma model [J]. Mol Imaging Biol, 2006, 8(6): 315-323.

[32] Wu Y, Cai W, Chen X. Near-infrared fluorescence imaging of tumor integrin αvβ3 expression with Cy7-labeled RGD multimers [J]. Mol Imaging Biol, 2006, 8(4): 226-236.

[33] Cai W, Shin DW, Chen K, et al. Peptide-labeled near-infrared quantum dots for imaging tumor vasculature in living subjects [J]. Nano Lett, 2006, 6(4): 669-676.

[34] Cai W, Chen K, Li ZB, et al. Dual-function probe for PET and near-infrared fluorescence imaging of tumor vasculature [J]. J Nucl Med, 2007, 48(11): 1862-1870.

基金

国家“ 重大新药创制” 科技重大专项制剂平台(2012ZX09304004)、上海市自然科学基金项目(09ZR1430900)

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