材料科学    Vol.5 No.3 (May 2015)

多肽修饰Fe3O4磁性纳米颗粒及其肿瘤细胞靶向性
Selectively Tumor Targeted Fe3O4 Magnetic Nanoparticles Modified with Peptide

作者: 尤 飞 , 尹光福 , 蒲曦鸣 ：四川大学材料科学与工程学院，四川 成都;

关键词: Fe3O4磁性纳米颗粒； 特异性多肽； 主动靶向； 肿瘤细胞； Fe3O4 Magnetic Nanoparticles； Specific Peptide； Active Targeting； Tumor Cells

摘要:
Fe3O4磁性纳米颗粒已被广泛的应用于肿瘤的成像与治疗，但限制其应用的一个主要因素是磁性纳米颗粒在肿瘤部位达不到足够的功能剂量。在磁性纳米颗粒表面偶联特异性靶向配体可使其结合于特定肿瘤细胞。目的：将特异性结合Fe3O4磁性纳米颗粒的短肽(TVNFKLY)与特异性结合卵巢肿瘤细胞A2780的短肽(QQTNWSL)合成的双功能多肽用于修饰Fe3O4磁性纳米颗粒，并研究其对正常细胞的毒性及对A2780细胞的靶向效果。方法：采用傅立叶转换红外光谱、热重分析、荧光显微镜等方法分析多肽与Fe3O4磁性纳米颗粒的结合，采用MTT法检测多肽结合后的Fe3O4磁性纳米颗粒的细胞毒性，并通过普鲁士蓝染色法验证靶向性。结果：合成的多肽(QQTNWSLTVNFKLY)能与Fe3O4磁性纳米颗粒结合，结合多肽后的纳米颗粒对L929等正常细胞无明显细胞毒性，对肿瘤细胞有较好的靶向性。结论：合成的双功能多肽能与Fe3O4磁性纳米颗粒结合并具有主动靶向A2780细胞的能力，具有潜在的应用价值。

Abstract: Fe3O4 magnetic nanoparticles (MNPs) have been widely used in tumor imaging and therapy. How-ever, low therapeutic concentration at tumor sites is one of the most important factors that limit their applications. MNPs conjugated with specific targeting ligands might selectively bind to specific tumor cells to increase the concentration of MNPs at tumor sites while the total dose decreased. Objective: Fe3O4 MNPs specific binding peptide (TVNFKLY) and ovarian tumor cells A2780 specific binding peptide (QQTNWSL) were conjugated together to form a bi-functional peptide, which was used to modify Fe3O4 MNPs, and the cytotoxicity and targeting ability of MNPs were investigated. Methods: Fourier transform infrared spectrometry, thermal analysis and fluorescence microscopy have been used to demonstrate the presence of peptide on the surface of Fe3O4 MNPs. MTT assays were employed to detect the cell viability. The targeting ability of Fe3O4 MNPs was verified by Prussian blue staining. Results: Synthesized peptide (QQTNWSLTVNFKLY) could bind to Fe3O4 MNPs, and Fe3O4 MNPs binding with peptide had no significant cytotoxicity to L929 cells and exhibited good targeting ability to tumor cells. Conclusion: The synthesized bi-functional peptide could bind to Fe3O4 MNPs, and the MNPs had better capability to target tumor cells.

文章引用: 尤 飞 , 尹光福 , 蒲曦鸣 (2015) 多肽修饰Fe3O4磁性纳米颗粒及其肿瘤细胞靶向性。 材料科学， 5， 111-118. doi: 10.12677/MS.2015.53016

参考文献

[1] Jordan, A., Scholz, R., Maier-Hauff, K., Johannsen, M., Wust, P., Nadobny, J., Schirra, H., Schmidt, H., Deger, S., Loening, S., et al. (2001) Presentation of a new magnetic field therapy system for the treatment of human solid tumors with magnetic fluid hyperthermia. Journal of Magnetism and Magnetic Materials, 225, 118-126.

[2] Sun, C., Lee, J.S.H. and Zhang, M. (2008) Magnetic nanoparticles in MR imaging and drug delivery. Advanced Drug Delivery Re-views, 60, 1252-1265.

[3] Veiseh, O., Gunn, J.W. and Zhang, M. (2010) Design and fabrication of magnetic nano-particles for targeted drug delivery and imaging. Advanced Drug Delivery Reviews, 62, 284-304.

[4] Karlsson, H.L., Gustafsson, J., Cronholm, P. and Moller, L. (2009) Size-dependent toxicity of metal oxide particles—A comparison between nano- and micrometer size. Toxicology Letters, 188, 112-118.

[5] Chang, Y.-K., Liu, Y.-P., Ho, J.H., Hsu, S.-C. and Lee, O.K. (2012) Amine-surface-modified superparamagnetic iron oxide nanoparticles interfere with diffe-rentiation of human mesenchymal stem cells. Journal of Orthopaedic Research, 30, 1499-1506.

[6] Hussain, S.M., Hess, K.L., Gearhart, J.M., Geiss, K.T. and Schlager, J.J. (2005) In vitro toxicity of nanoparticles in BRL 3A rat liver cells. Toxicology in Vitro, 19, 975-983.

[7] Xie, J., Chen, K., Lee, H.-Y., Xu, C., Hsu, A.R., Peng, S., Chen, X. and Sun, S. (2008) Ultrasmall c(RGDyK)-coated Fe3O4 nanoparticles and their specific targeting to integrin alphavbeta3-rich tumor cells. Journal of the American Chemical Society, 130, 7542-7543.

[8] Valetti, S., Maione, F., Mura, S., Stella, B., Desmaele, D., Noiray, M., Vergnaud, J., Vauthier, C., Cattel, L., Giraudo, E., et al. (2014) Peptide-functionalized nanoparticles for selective targeting of pancreatic tumor. Journal of Controlled Release, 192, 29-39.

[9] Gan, Z.-F., Jiang, J.-S., Yang, Y., Du, B., Qian, M. and Zhang, P. (2008) Immobilization of homing peptide on magnetite nanoparticles and its specificity in vitro. Journal of Biomedical Materials Research Part A, 84A, 10-18.

[10] Yang, X., Chen, Y., Yuan, R., Chen, G., Blanco, E., Gao, J. and Shuai, X. (2008) Folate-encoded and Fe3O4-loaded polymeric micelles for dual targeting of cancer cells. Polymer, 49, 3477-3485.

[11] Zheng, S.W., Huang, M., Hong, R.Y., Deng, S.M., Cheng, L.F., Gao, B. and Badami, D. (2014) RGD-conjugated iron oxide magnetic nanoparticles for magnetic resonance imaging contrast enhancement and hyperthermia. Journal of Biomaterials Applications, 28, 1051-1059.

[12] Golec, P., Karczewska-Golec, J., Los, M. and Wegrzyn, G. (2012) Novel ZnO-binding peptides obtained by the screening of a phage display peptide library. Journal of Nanoparticle Research, 14, 1218.

[13] Ploss, M., Facey, S.J., Bruhn, C., Zemel, L., Hofmann, K., Stark, R.W., Albert, B. and Hauer, B. (2014) Selection of peptides binding to metallic borides by screening M13 phage display libraries. BMC Biotechnology, 14, 12.

[14] Guo, Y., Ma, C., Li, C., Wu, J., Zhang, D., Han, J., Wang, Q., Xu, J., Lu, S. and Hou, Y. (2014) Screening and identification of a specific peptide binding to hepatocellular carcinoma cells from a phage display peptide library. Journal of Peptide Science, 20, 196-202.

[15] Ma, C., Yin, G., Yan, D., He, X., Zhang, L., Wei, Y. and Huang, Z. (2013) A novel peptide specifically targeting ovarian cancer identified by in vivo phage display. Journal of Peptide Science, 19, 730-736.

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