受体介导靶向恶性脑胶质瘤递药系统的研究进展
Research Progress in Malignant Glioma Tar-geting Delivery System Mediated with Re-ceptors
DOI: 10.12677/PI.2018.72006, PDF,    科研立项经费支持
作者: 汪红艳, 刘 煜*：中国药科大学，江苏 南京
关键词: 恶性胶质瘤；血脑屏障；受体；靶向递药；Malignant Glioma； Blood-Brain Barrier； Receptor； Targeting Drugs Delivery
摘要: 恶性脑胶质瘤全球发病率为3.20/100,000，患者中位生存期不足2年，5年生存率仅9.8%，治疗后复发率几近100%，且目前仍无有效治疗方案。由于恶性胶质瘤存在浸润性生长的特点，手术无法根治，对于常用化疗药物又普遍存在内在抗拒性，导致化疗疗效有限。由于血脑屏障的存在，几乎全部的大分子药物以及98%以上的小分子药物都无法到达病灶，而受体介导的转运方式利用了血脑屏障自身的特性，通过内源性血脑屏障转运系统有效的跨越血脑屏障并靶向恶性胶质瘤进行药物输送，为胶质瘤的治疗提供了一种更为安全且有效的递药策略。
Abstract: The worldwide cancer incidence of malignant encephalic glioma is 3.20/100,000, the median survival for patients is less than 2 years and 9.8% of patients survived five years post diagnosis, with near 100% relapse rates and currently limited treatment options. Operations and chemotherapy drugs have limited efficacy for aggressive glioma with intrinsic resistance to drugs. Almost the whole of macromolecule and 98% of small-molecule drugs are unable to across blood-brain barrier. The receptor mediated endocytosis is one of the endogenous transporting channels, xenobiotics across blood-brain barrier and target glioma by taking advantages of cells. It provides a safer and more effective drugs delivery strategy for cancer treatment.
文章引用：汪红艳, 刘煜. 受体介导靶向恶性脑胶质瘤递药系统的研究进展[J]. 药物资讯, 2018, 7(2): 27-32. https://doi.org/10.12677/PI.2018.72006

参考文献

[1] Louis, D.N., Perry, A., Reifenberger, G., et al. (2016) The 2016 World Health Organization Classification of Tumors of the Central Nervous System: A Summary. Acta Neuropathologica, 131, 803-820. [Google Scholar] [CrossRef] [PubMed]
[2] Ostrom, Q. T., Gittleman, H., Stetson, L., et al. (2015) Current Understanding and Treatment of Gliomas. Springer International Publishing, Switzerland, 1-14.
[3] Filley, A.C., Henriquez, M. and Dey, M. (2017) Recurrent Glioma Clinical Trial, CheckMate-143: The Game Is Not Over Yet. Oncotarget, 8, 91779-91794. [Google Scholar] [CrossRef] [PubMed]
[4] Lieberman, F. (2017) Glioblastoma Update: Molecular Biology, Diagnosis, Treatment, Response Assessment, and Translational Clinical Trials. F1000Research, 6, 1892. [Google Scholar] [CrossRef] [PubMed]
[5] Stupp, R., Hegi, M.E., Mason, W.P., et al. (2009) Effects of Radiotherapy with Concomitant and Adjuvant Temozolomide versus Radiotherapy Alone on Survival in Glioblastoma in a Randomised Phase III Study: 5-Year Analysis of the EORTC-NCIC Trial. The Lancet Oncology, 10, 459-466. [Google Scholar] [CrossRef] 
[6] Hu, B., Wang, Q., Wang, Y.A., et al. (2016) Epigenetic Activation of WNT5A Drives Glioblastoma Stem Cell Differentiation and Invasive Growth. Cell, 167, 1281-1295. [Google Scholar] [CrossRef] [PubMed]
[7] Tsutsumi, Y., Tsunoda, S., Kamada, H., et al. (1997) PEGylation of Interleukin-6 Effectively Increases Its Thrombopoietic Potency. Thrombosis and Haemostasis, 77, 168-173.
[8] Gliadel (2018) Important Safety Imformation of GLIADEL Wafer. http://gliadel.com/hcp/index.php
[9] Underwood, E. (2015) Ultrasound Therapies Target Brain Cancers and Alzheimer’s Disease. Science, 347, 1186-1187. [Google Scholar] [CrossRef] [PubMed]
[10] Patel, M.M. and Patel, B.M. (2017) Crossing the Blood-Brain Barrier: Recent Advances in Drug Delivery to the Brain. Cns Drugs, 31, 109-133. [Google Scholar] [CrossRef] [PubMed]
[11] Zhang, Y. and Pardridge, W.M. (2006) Blood-Brain Barrier Targeting of BDNF Improves Motor Function in Rats with Middle Cerebral Artery Occlusion. Brain Research, 1111, 227-229. [Google Scholar] [CrossRef] [PubMed]
[12] Wang, Y.Y., Lui, P.C. and Li, J.Y. (2017) Receptor-Mediated Therapeutic Transport across the Blood-Brain Barrier. Immunotherapy, 1, 983-993. [Google Scholar] [CrossRef] [PubMed]
[13] 魏晓丽. 稳定性多肽介导跨血脑屏障的脑胶质瘤双重靶向递药系统研究[D]: [博士学位论文]. 上海: 复旦大学药学院, 2014.
[14] O’Donnell, K.A., Yu, D., Zeller, K.I., et al. (2006) Activation of Transferrin Receptor 1 by c-Myc Enhances Cellular Proliferation and Tumorigene-sis. Molecular and Cellular Biology, 26, 2373-2386.
[15] Hogemann-Savellano, D., Bos, E., Blondet, C., et al. (2003) The Transfer-ring Receptor: A Potential Molecular Imaging Marker for Human Cancer. Neoplasia, 5, 495-506.
[16] 吴光勇. MIR分子影像学报告基因Tfr在胶质瘤中的表达及质粒的构建与鉴定[D]: [博士学位论文]. 湖南: 中南大学湘雅医院, 2007.
[17] Chen, Y., Zhang, M., Jin, H., et al. (2017) Glioma Dual-Targeting Nanohybrid Protein Toxin Constructed by Intein-Mediated Site-Specific Ligation for Multistage Booster Delivery. Theranostics, 7, 3489-3503. [Google Scholar] [CrossRef] [PubMed]
[18] Liu, S., Guo, Y., Huang, R., et al. (2012) Gene and Doxorubicin Co-Delivery System for Targeting Therapy of Glioma. Biomaterials, 33, 4907-4916. [Google Scholar] [CrossRef] [PubMed]
[19] Wang, Z., Zhao, Y., Jiang, Y., et al. (2015) Enhanced Anti-Ischemic Stroke of ZL006 by T7-Conjugated PEGylated Liposomes Drug Delivery System. Scientific Reports, 5, Article No. 12651. [Google Scholar] [CrossRef] [PubMed]
[20] Zong, T., Mei, L., Gao, H., et al. (2014) Enhanced Glioma Targeting and Penetration by Dual-Targeting Liposome Co-Modified with T7 and TAT. Journal of Pharmaceutical Sciences, 103, 3891-3901. [Google Scholar] [CrossRef] [PubMed]
[21] Vu, K., Tham, R. and Uhrig, J. (2014) Invasion of the Central Nervous System by Cryp-tococcus Neoformans Requires a Secreted Fungal Metalloprotease. mBio, 5, e01101-e01114. [Google Scholar] [CrossRef] 
[22] Demeule, M., Régina, A., Ché, C., et al. (2008) Identification and Design of Peptides as a New Drug Delivery System for the Brain. Journal of Pharmacology and Experimental Therapeutics, 24, 1064-1072.
[23] Yang, Z.Z., Li, J.Q., Wang, Z.Z., et al. (2014) Tumor-Targeting Dual Peptides Modified Cationic Liposomes for Delivery of siRNA and Docetaxel to Gliomas. Biomaterials, 35, 5226-5239. [Google Scholar] [CrossRef] [PubMed]
[24] Yainoy, S., Houbloyfa, P., Eiamphungporn, W., et al. (2014) Engineering of Chimeric Catalase-Angiopep-2 for Intracellular Protection of Brain Endothelial Cells against Oxidative Stress. International Journal of Biological Macromolecules, 68, 60-66. [Google Scholar] [CrossRef] [PubMed]
[25] Sarkar, G., Curran, G.L., Sarkaria, G.N., et al. (2014) Peptide Carrier-Mediated Non-Covalent Delivery of Unmodified Cisplatin, Methotrexate and Other Agents via In-travenous Route to the Brain. PLoS ONE, 9, e97655. [Google Scholar] [CrossRef] [PubMed]
[26] Ben-Zvi, A., Lacoste, B., Kur, E., et al. (2014) MSFDA Is Critical for the Formation and Function of the Blood Brain Barrier. Nature, 509, 507-511. [Google Scholar] [CrossRef] [PubMed]