药学学报, 2013, 48(12): 1763-1770
王蔚芹, 张振海, 周建平, 庞卉, 吕慧侠. 用于肿瘤靶向治疗与诊断的糖结合物研究进展[J]. 药学学报, 2013, 48(12): 1763-1770.
WANG Wei-qin, ZHANG Zhen-hai, ZHOU Jian-ping, PANG Hui, LÜ Hui-xia. An overview of glycoconjugates for cancer targeting therapy and diagnosis[J]. Acta Pharmaceutica Sinica, 2013, 48(12): 1763-1770.

王蔚芹1,2, 张振海1, 周建平1, 庞卉2, 吕慧侠1
1. 中国药科大学药剂教研室, 江苏 南京 210009;
2. 江苏省食品药品检验所, 江苏 南京 210008
关键词:    葡萄糖      葡萄糖转运体      糖结合物     
An overview of glycoconjugates for cancer targeting therapy and diagnosis
WANG Wei-qin1,2, ZHANG Zhen-hai1, ZHOU Jian-ping1, PANG Hui2, LÜ Hui-xia1
1. Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, China;
2. Jiangsu Institute for Food and Drug Control, Nanjing 210008, China
Because of the changed metabolic behaviors of cancer cells, tumor cells uptake a corresponding larger amount of glucose in physiological condition when compared with normal cells. And they were prone to metabolize glucose for generating energy in anaerobic glycolysis ways in order to grow quickly. Anaerobic glycolysis consumes more glucose than aerobic way when the same amount of energy is obtained, which also results in large demand of glucose in tumor cells. This review briefly describes therapy methods related to characteristic mentioned above, and summarizes the research progress of drugs, diagnostic reagents and carriers conjugated with glucose, glucose derivatives or other kinds of sugars for cancer targeting. Furthermore, typically relative research reports from 2012 till now were listed and analyzed.
Key words:    glucose    glucose transporter    glycoconjugates   
收稿日期: 2013-06-14
通讯作者: 庞卉, 吕慧侠
Email: lvhuixia@163.com;panghui77@yahoo.com
PDF(623KB) Free
王蔚芹  在本刊中的所有文章
张振海  在本刊中的所有文章
周建平  在本刊中的所有文章
庞卉  在本刊中的所有文章
吕慧侠  在本刊中的所有文章

[1] Chiaradonna F, Moresco RM, Airoldi C, et al. From cancer metabolism to new biomarkers and drug targets[J]. Biotechnol Adv, 2012, 30: 30-51.
[2] Szablewski L. Expression of glucose transporters in cancers[J]. Biochim Biophys Acta, 2012, 1835: 164-169.
[3] Mathews EH, Liebenberg L, Pelzer R. High-glycolytic cancers and their interplay with the body's glucose demand and supply cycle[J]. Med Hypotheses, 2011, 76: 157-165.
[4] Liu Y, Zhang WH, Cao YY, et al. Small compound inhibitors of basal glucose transport inhibit cell proliferation and induce apoptosis in cancer cells via glucose-deprivation-like mechanisms[J]. Cancer Lett, 2010, 298: 176-185.
[5] Stein M, Lin HX, Jeyamohan C, et al. Targeting tumor metabolism with 2-deoxyglucose in patients with castrate-resistant prostate cancer and advanced malignancies[J]. Prostate, 2010, 70: 1388-1394.
[6] Chen JQ, Russo J. Dysregulation of glucose transport, glycolysis, TCA cycle and glutaminolysis by oncogenes and tumor suppressors in cancer cells[J]. Biochim Biophys Acta, 2012, 1826: 370-384.
[7] Mogi A, Koga K, Aoki M, et al. Expression and role of GLUT-1, MCT-1, and MCT-4 in malignant pleural mesothelioma[J]. Virchows Arch, 2013, 462: 83-93.
[8] Ganapathy V, Thangaraju M, Prasad PD. Nutrient transporters in cancer: relevance to Warburg hypothesis and beyond[J]. Pharmacol Therapeut, 2009, 121: 29-40.
[9] Nijsten MWN, van Dam GM. Hypothesis: using the Warburg effect against cancer by reducing glucose and providing lactate[J]. Med Hypotheses, 2009, 73: 48-51.
[10] Yamashita F, Hashida M. Pharmacokinetic considerations for targeted drug delivery[J]. Adv Drug Deliv Rev, 2013, 65: 139-147.
[11] Pohl J, Bertram B, Hilgard P, et al. D-19575—a sugar-linked isophosphoramide mustard derivative exploiting transmembrane glucose transport[J]. Cancer Chemoth Pharm, 1995, 35: 364-370.
[12] Sun YM. Preclinical Pharmacokinetic Study of Glufosfamide (葡磷酰胺临床前药物代谢与动力学研究)[D]. Shenyang: Shenyang Pharmaceutical University, 2006.
[13] Calvaresi EC, Hergenrother PJ. Glucose conjugation for the specific targeting and treatment of cancer[J]. J Chem Sci, 2013, 4: 2319-2333.
[14] Ekholm FS, Berényi Á, Lagerquist L, et al. Cytotoxic activity of some glycoconjugates including saponins and anthracyclines[J]. Carbohyd Res, 2012, 356: 295-298.
[15] Liu PH, Lu YH, Gao QX, et al. Highly water-soluble platinum (II) complexes as GLUT substrates for targeted therapy: improved anticancer efficacy and transporter-mediated cytotoxic properties[J]. Chem Commun, 2013, 49: 2421-2423.
[16] Wang AQ, Chen YQ, Chen WR, et al. Novel 2DG-based harmine derivatives for targeted cancer therapy[C]. International Society for Optics and Photonics, 2013: 85820V.
[17] Li SW, Tian JM, Jin J, et al. Targeted biodistribution of aminoglucose-modified doxorubicin[J]. J China Pharm Univ (中国药科大学学报), 2012, 43: 266-270.
[18] Cao J, Cui SS, Li SW, et al. Targeted cancer therapy with a 2-deoxyglucose-based adriamycin complex[J]. Cancer Res, 2013, 73: 1362-1373.
[19] Pawar SK, Badhwar AJ, Kharas F, et al. Design, synthesis and evaluation of N-acetyl glucosamine (NAG)-PEG-doxorubicin targeted conjugates for anticancer delivery[J]. Int J Pharm, 2012, 436: 183-193.
[20] Keereweer S, Sterenborg HJCM, Kerrebijn JDF, et al. Image-guided surgery in head and neck cancer: current practice and future directions of optical imaging[J]. Head Neck, 2012, 34: 120-126.
[21] Geng XD, Shan XH, Xiong F, et al. Preparation of a glucose receptor-mediated tumor targeting 2-DG-conjugated superparamagnetic iron oxide nanoparticles and its in vitro experimental study[J]. Shandong Med J (山东医药), 2012, 52: 1-4.
[22] Kumar P, Shustov G, Liang H, et al. Design, synthesis, and preliminary biological evaluation of 6-O-glucose-azomycin adducts for diagnosis and therapy of hypoxic tumors[J]. J Med Chem, 2012, 55: 6033-6046.
[23] Ballut S, Makky A, Chauvin B, et al. Tumor targeting in photodynamic therapy. From glycoconjugated photosensitizers to glycodendrimeric one. Concept, design and properties[J]. Org Biomol Chem, 2012, 10: 4485-4495.
[24] Zhang W, Chen Y, Guo DJ, et al. The synthesis of a d-glucosamine contrast agent, Gd-DTPA-DG, and its application in cancer molecular imaging with MRI[J]. Eur J Radiol, 2011, 79: 369-374.
[25] Jiang SH, Ge YR, Shan XH, et al. Glucose-receptor targeting long-circulating Gd-DTPA liposomes targeting to tumor cell[J]. Chin Hosp Pharm J (中国医院药学杂志), 2008, 28: 1916-1918.
[26] Lü F, Li YZ, Cao B, et al. Galactose substituted zinc phthalocyanines as near infrared fluorescence probes for liver cancer imaging[J]. J Mater Sci Mater Med, 2013, 24: 811-819.
[27] Lü F, He XJ, Wu L, et al. Lactose substituted zinc phthalocyanine: a near infrared fluorescence imaging probe for liver cancer targeting[J]. Bioorg Med Chem Lett, 2013, 23: 1878-1882.
[28] Jain K, Kesharwani P, Gupta U, et al. A review of glycosylated carriers for drug delivery[J]. Biomaterials, 2012, 33: 4166-4186.
[29] Huang G. Glyconanoparticles-an update[J]. Curr Med Chem, 2013, 20: 782-788.
[30] Guo R, Yao Y, Cheng GC, et al. Synthesis of glycoconjugated poly (amindoamine) dendrimers for targeting human liver cancer cells[J]. RSC Advances, 2012, 2: 99-102.
[31] Agarwal A, Gupta U, Asthana A, et al. Dextran conjugated dendritic nanoconstructs as potential vectors for anti-cancer agent[J]. Biomaterials, 2009, 30: 3588-3596.
[32] Matsui M, Shimizu Y, Kodera Y, et al. Targeted delivery of oligomannose-coated liposome to the omental micrometastasis by peritoneal macrophages from patients with gastric cancer[J]. Cancer Sci, 2010, 101: 1670-1677.
[33] Wang J, Yin C, Tang G, et al. Glucose-functionalized multidrug-conjugating nanoparticles based on amphiphilic terpolymer with enhanced anti-tumorous cell cytotoxicity[J]. Int J Pharm, 2013, 441: 291-298.
[34] Ozkaya F, Unak P, Medine E I, et al. 18FDG conjugated magnetic nanoparticle probes: synthesis and in vitro investigations on MCF-7 breast cancer cells[J]. J Radioanal Nucl Chem, 2013, 295: 1789-1796.
[35] Xiong F, Zhu ZY, Xiong C, et al. Preparation, characterization of 2-deoxy-D-glucose functionalized dimercaptosuccinic acid-coated maghemite nanoparticles for targeting tumor cells[J]. Pharmaceut Res, 2012, 29: 1087-1097.
[36] Shan XH, Hu H, Xiong F, et al. Targeting Glut1-overexpressing MDA-MB-231 cells with 2-deoxy-d-g1ucose modified SPIOs[J]. Eur J Radiol, 2012, 81: 95-99.
[37] Li HJ, Fan W, Li XK, et al. Design and synthesis of glucose-cholesterol as ligand for brain targeting liposomes[J]. West China J Pharm Sci (华西药学杂志), 2010, 25: 251-253.
[38] Fernández C, Nieto O, Rivas E, et al. Synthesis and biological studies of glycosyl dopamine derivatives as potential antiparkinsonian agents[J]. Carbohyd Res, 2000, 327: 353-365.
[39] Shann SY, Lau CM, Barham WJ, et al. Macrophage-specific RNA interference targeting via “click”, mannosylated polymeric micelles[J]. Mol Pharmaceut, 2013, 10: 975-987.
[40] Villa R, Cerroni B, Viganò L, et al. Targeted doxorubicin delivery by chitosan-galactosylated modified polymer microbubbles to hepatocarcinoma cells[J]. Colloids Surf B: Biointerfaces, 2013, 110: 434-442.
[41] Ma YX, Chen YQ, Cui SS, et al. Preparation and Characterization of a Drug Carrier for Hepatocellular Carcinoma Targeting[C]. International Society for Optics and Photonics, 2013: 85820U.