半乳糖修饰的海藻酸纳米载体构建及其抗肿瘤功效
Fabrication of Galactosylated Alginate Nanoparticles as Drug Delivery System for Hepatocellular Carcinoma
DOI: 10.12677/NAT.2016.62004, PDF,   
作者: 李政雄, 吴晓盈*：复旦大学生命科学学院，遗传国家重点实验室，上海
关键词: 肝癌；海藻酸纳米粒；半乳糖；药物递送；DOX；Hepatocellular Carcinoma； Alginate Nanoparticle； Galactose； Drug Delivery； DOX
摘要: 本文设计制备肝靶向聚合物纳米粒–半乳糖(Gal)修饰海藻酸酯(HA-Gal)纳米粒，以阿霉素(DOX)为抗肿瘤模型药物制备载药纳米粒(DOX/HA-Gal)，研究DOX/HA-Gal的理化性质、载药与释药、体外细胞增殖抑制，考察不同Gal接枝比对体外抗肿瘤功效的影响。结果表明DOX/HA-Gal为大小均一的球形粒子，水合动力学粒径为180-250nm，荷负电(<−30 mV)；随Gal接枝比的增大，DOX/HA-Gal的粒径增大，Zeta电势升高，包封率增加，肿瘤细胞杀伤率提高。
Abstract: The alginate derivative naonoparticles modified by galactose (HA-Gal) with various galactose (Gal) substitution degrees were synthesized to evaluate their potential for hepatocellular carcinoma (HCC) targeting. Their physicochemical characteristics were investigated. Doxorubicin hydrochloride (DOX) as a model antitumor drug was incorporated into the HA-Gal. The in vitro drug release and antitumor capability of DOX loaded HA-Gal (DOX/HA-Gal) with different Gal substitution degrees were evaluated. Negatively charged DOX/HA-Gal appeared monodisperse and spherical in shape with a size range of 180 - 250 nm, and their Zeta potentials were above 30 mV (absolute value). The size, Zeta potentials, encapsulation efficiency and in vitro cytotoxicity of HA-Gal were increased with the increment in Gal substitution degree.
文章引用：李政雄, 吴晓盈. 半乳糖修饰的海藻酸纳米载体构建及其抗肿瘤功效[J]. 纳米技术, 2016, 6(2): 23-32. https://dx.doi.org/10.12677/NAT.2016.62004

参考文献

[1] Ferlay, J., Shin, H.-R., Bray, F., Forman, D., Mathers, C. and Parkin, D.M. (2010) Estimates of Worldwide Burden of Cancer in 2008: GLOBOCAN 2008. International Journal of Cancer, 127, 2893-2917. http://dx.doi.org/10.1002/ijc.25516 [Google Scholar] [CrossRef] [PubMed]
[2] Ma, S., Jiao, B., Liu, X., Yi, H., Kong, D., Gao, L., Zhao, G., Yang, Y. and Liu, X. (2010) Approach to Radiation Therapy in Hepatocellular Carcinoma. Cancer Treatment Reviews, 36, 157-163. http://dx.doi.org/10.1016/j.ctrv.2009.11.008 [Google Scholar] [CrossRef] [PubMed]
[3] Ma, P. and Mumper, R.J. (2013) Anthracycline Nano-Delivery Systems to Overcome Multiple Drug Resistance: A Comprehensive Review. Nano Today, 8, 313-331. http://dx.doi.org/10.1016/j.nantod.2013.04.006 [Google Scholar] [CrossRef] [PubMed]
[4] Yang, J.-S., Xie, Y.-J. and He, W. (2011) Research Progress on Chemical Modification of Alginate: A Review. Carbohydrate Polymers, 84, 33-39. http://dx.doi.org/10.1016/j.carbpol.2010.11.048 [Google Scholar] [CrossRef] 
[5] Li, Q., Liu, C.-G. and Yu, Y. (2015) Separation of Monodisperse Alginate Nanoparticles and Effect of Particle Size on Transport of Vitamin E. Carbohydrate Polymers, 124, 274-279. http://dx.doi.org/10.1016/j.carbpol.2015.02.007 [Google Scholar] [CrossRef] [PubMed]
[6] Yang, J.S., Zhou, Q.Q. and He, W. (2013) Amphipathicity and Self-Assembly Behavior of Amphiphilic Alginate Esters. Carbohydrate Polymers, 92, 223-227. http://dx.doi.org/10.1016/j.carbpol.2012.08.100 [Google Scholar] [CrossRef] [PubMed]
[7] Wang, M. and Thanou, M. (2010) Targeting Nanoparticles to Cancer. Pharmacological Research, 62, 90-99. http://dx.doi.org/10.1016/j.phrs.2010.03.005 [Google Scholar] [CrossRef] [PubMed]
[8] Byrne, J.D., Betancourt, T. and Brannon-Peppas, L. (2008) Active Targeting Schemes for Nanoparticle Systems in Cancer Therapeutics. Advanced Drug Delivery Reviews, 60, 1615-1626. http://dx.doi.org/10.1016/j.addr.2008.08.005 [Google Scholar] [CrossRef] [PubMed]
[9] D’Souza, A.A. and Devarajan, P.V. (2015) Asialoglycoprotein Receptor Mediated Hepatocyte Targeting—Strategies and Applications. Journal of Controlled Release, 203, 126-139. http://dx.doi.org/10.1016/j.jconrel.2015.02.022 [Google Scholar] [CrossRef] [PubMed]
[10] Zhang, X.Q., Wang, X.L., Zhang, P.C., Liu, Z.L., Zhuo, R.X., Mao, H.Q. and Leong, K.W. (2005) Galactosylated Ternary DNA/Polyphosphoramidate Nanoparticles Mediate High Gene Transfection Efficiency in Hepatocytes. Journal of Controlled Release, 102, 749-763. http://dx.doi.org/10.1016/j.jconrel.2004.10.024 [Google Scholar] [CrossRef] [PubMed]
[11] Yang, J.S. and He, W. (2012) Synthesis of Lauryl Grafted Sodium Alginate and Optimization of the Reaction Conditions. International Journal of Biological Macromolecules, 50, 428-431. http://dx.doi.org/10.1016/j.ijbiomac.2011.12.027 [Google Scholar] [CrossRef] [PubMed]
[12] Lin, A., Liu, Y., Huang, Y., Sun, J., Wu, Z., Zhang, M. and Ping, Q. (2008) Glycyrrhizin Surface-Modified Chitosan Nanoparticles for Hepatocyte-Targeted Delivery. International Journal of Pharmaceutics, 359, 247-253. http://dx.doi.org/10.1016/j.ijpharm.2008.03.039 [Google Scholar] [CrossRef] [PubMed]
[13] Huang, M., Fong, C.W., Khor, E. and Lim, L.Y. (2005) Transfection Efficiency of Chitosan Vectors: Effect of Polymer Molecular Weight and Degree of Deacetylation. Journal of Controlled Release, 106, 391-406. http://dx.doi.org/10.1016/j.jconrel.2005.05.004 [Google Scholar] [CrossRef] [PubMed]

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