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Journal of Zhejiang University SCIENCE B 2011 Vol.12 No.9 P.720-729

http://doi.org/10.1631/jzus.B1000307


Polyethylenimine-cyclodextrin-tegafur conjugate shows anti-cancer activity and a potential for gene delivery


Author(s):  Qi-da Hu, Hui Fan, Wei-jian Lou, Qing-qing Wang, Gu-ping Tang

Affiliation(s):  Institute of Chemical Biology and Pharmaceutical Chemistry, Zhejiang University, Hangzhou 310028, China, Department of Pharmacy, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, China, Institute of Immunology, Zhejiang University, Hangzhou 310058, China, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China

Corresponding email(s):   tangguping@yahoo.com.cn

Key Words:  Polyethylenimine, β, -Cyclodextrin, Tegafur, Co-delivery, Gene therapy


Qi-da Hu, Hui Fan, Wei-jian Lou, Qing-qing Wang, Gu-ping Tang. Polyethylenimine-cyclodextrin-tegafur conjugate shows anti-cancer activity and a potential for gene delivery[J]. Journal of Zhejiang University Science B, 2011, 12(9): 720-729.

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author="Qi-da Hu, Hui Fan, Wei-jian Lou, Qing-qing Wang, Gu-ping Tang",
journal="Journal of Zhejiang University Science B",
volume="12",
number="9",
pages="720-729",
year="2011",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B1000307"
}

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%T Polyethylenimine-cyclodextrin-tegafur conjugate shows anti-cancer activity and a potential for gene delivery
%A Qi-da Hu
%A Hui Fan
%A Wei-jian Lou
%A Qing-qing Wang
%A Gu-ping Tang
%J Journal of Zhejiang University SCIENCE B
%V 12
%N 9
%P 720-729
%@ 1673-1581
%D 2011
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B1000307

TY - JOUR
T1 - Polyethylenimine-cyclodextrin-tegafur conjugate shows anti-cancer activity and a potential for gene delivery
A1 - Qi-da Hu
A1 - Hui Fan
A1 - Wei-jian Lou
A1 - Qing-qing Wang
A1 - Gu-ping Tang
J0 - Journal of Zhejiang University Science B
VL - 12
IS - 9
SP - 720
EP - 729
%@ 1673-1581
Y1 - 2011
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B1000307


Abstract: 
polyethylenimine-Cyclodextrin-tegafur (PEI-CyD-tegafur) conjugate was synthesized as a novel multifunctional prodrug of tegafur for co-delivery of chemotherapeutic agent tegafur and enhanced green fluorescent protein (EGFP) reporter plasmid DNA. Conjugation of tegafur to PEI-CyD via chemical linkage was characterized by 1H NMR spectrometry and ultraviolet (UV) spectrometry. PEI-CyD-tegafur was able to condense plasmid DNA into complexes of around 150 nm with positive charge at the N/P ratio of 25, in accordance with electron microscopy observation of compact and monodisperse nanoparticles. The results of in vitro experiments showed enhanced cytotoxicity and considerable transfection efficiency in B16F10 cell line. Therefore, PEI-CyD-tegafur may have great potential as a co-delivery system with anti-cancer activity and potential for gene delivery.

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article

Reference

[1]Akahoshi, K., Chijiiwa, Y., Hamada, S., Hara, K., Nakamura, K., Nawata, H., Matsui, N., 1998. Complete response of early gastric cancer to uracil and tegafur. J. Gastroenterol., 33(6):864-867.

[2]Akay, S., Ozutemiz, O., Doganavsargil, B., 2004. Severe colitis after administration of UFT chemotherapy for temporal bone carcinoma. Expert Opin. Drug Saf., 3(2):89-92.

[3]Arias, J.L., Gallardo, V., Ruiz, M.A., Delgado, A.V., 2007. Ftorafur loading and controlled release from poly(ethyl-2-cyanoacrylate) and poly(butylcyanoacrylate) nanospheres. Int. J. Pharm., 337(1-2):282-290.

[4]Arias, J.L., Linares-Molinero, F., Gallardo, V., Delgado, A.V., 2008a. Study of carbonyl iron/poly(butylcyanoacrylate) (core/shell) particles as anticancer drug delivery systems: Loading and release properties. Eur. J. Pharm. Sci., 33(3):252-261.

[5]Arias, J.L., Ruiz, M.A., Gallardo, V., Delgado, A.V., 2008b. Tegafur loading and release properties of magnetite/ poly(alkylcyanoacrylate) (core/shell) nanoparticles. J. Controll. Release, 125(1):50-58.

[6]Cao, S., Baccanari, D.P., Joyner, S.S., Davis, S.T., Rustum, Y.M., Spector, T., 1995. 5-Ethynyluracil (776C85): effects on the antitumor activity and pharmacokinetics of tegafur, a prodrug of 5-fluorouracil. Cancer Res., 55(24):6227-6230.

[7]Chen, A.M., Zhang, M., Wei, D., Stueber, D., Taratula, O., Minko, T., He, H., 2009. Co-delivery of doxorubicin and Bcl-2 siRNA by mesoporous silica nanoparticles enhances the efficacy of chemotherapy in multidrug-resistant cancer cells. Small, 5(23):2673-2677.

[8]Engel, D., Nudelman, A., Tarasenko, N., Levovich, I., Makarovsky, I., Sochotnikov, S., Tarasenko, I., Rephaeli, A., 2008. Novel prodrugs of tegafur that display improved anticancer activity and antiangiogenic properties. J. Med. Chem., 51(2):314-323.

[9]Friedman, M.A., Ignoffo, R.J., 1980. A review of the United States clinical experience of the fluoropyrimidine, ftorafur (NSC-148958). Cancer Treat. Rev., 7(4):205-213.

[10]He, Z.J., Chen, W.B., Zhang, C.X., Zhou, Z.H., Tang, C.C., 2000. Synthesis of novel optically active cyclic phospholipid conjugates of tegafur and uridine starting from L-serine. Phosphorus Sulfur Silicon Rel. Elem., 160(1):223-232.

[11]Huang, H., Yu, H., Tang, G., Wang, Q., Li, J., 2010. Low molecular weight polyethylenimine cross-linked by 2-hydroxypropyl-γ-cyclodextrin coupled to peptide targeting HER2 as a gene delivery vector. Biomaterials, 31(7):1830-1838.

[12]Malet-Martino, M., Martino, R., 2002. Clinical studies of three oral prodrugs of 5-fluorouracil (capecitabine, UFT, S-1): a review. Oncologist, 7(4):288-323.

[13]Mintzer, M.A., Simanek, E.E., 2009. Nonviral vectors for gene delivery. Chem. Rev., 109(2):259-302.

[14]Ota, K., Taguchi, T., Kimura, K., 1988. Report on nationwide pooled data and cohort investigation in UFT phase II study. Cancer Chemother. Pharmacol., 22(4):333-338.

[15]Seishima, M., Izumi, T., Kanoh, H., 2000. Raynaud’s phenomenon possibly induced by a compund drug of tegafur and uracil. Eur. J. Dermatol., 10(1):55-58.

[16]Shi, D.Q., Chen, Q., Li, Z.H., Liu, X.P., 2005. Synthesis of novel phosphoramide-tegafur derivatives containing aminopropylsilatrane. Phosphorus Sulfur Silicon Rel. Elem., 180(7):1621-1627.

[17]Shitara, K., Munakata, M., Koizumi, W., Sakata, Y., 2007. A case of suspected S-1 induced interstitial pneumonia. Jpn. J. Cancer Chemother., 34(4):619-622 (in Japanese).

[18]Stokes, D.M., Paul, B., Alderfer, J.L., Wollman, R.M., Srikrishnan, T., 2002. Synthesis, structure, and conformation of anti-tumor agents in the solid and solution states: hydroxyl derivatives of Ftorafur. Nucleos. Nucleot. Nucleic Acids, 21(11-12):863-882.

[19]Tada, Y., Takiguchi, Y., Fujikawa, A., Kitamura, A., Kurosu, K., Hiroshima, K., Sakao, S., Kasahara, Y., Tanabe, N., Tatsumi, K., et al., 2007. Pulmonary toxicity by a cytotoxic agent, S-1. Internal Med., 46(15):1243-1246.

[20]Takechi, T., Nakano, K., Uchida, J., Mita, A., Toko, K., Takeda, S., Unemi, N., Shirasaka, T., 1997. Antitumor activity and low intestinal toxicity of S-1, a new formulation of oral tegafur, in experimental tumor models in rats. Cancer Chemother. Pharmacol., 39(3):205-211.

[21]Tang, G.P., Guo, H.Y., Alexis, F., Wang, X., Zeng, S., Lim, T.M., Ding, J., Yang, Y.Y., Wang, S., 2006. Low molecular weight polyethylenimines linked by β-cyclodextrin for gene transfer into the nervous system. J. Gene Med., 8(6):736-744.

[22]Wang, Y., Gao, S., Ye, W.H., Yoon, H.S., Yang, Y.Y., 2006. Co-delivery of drugs and DNA from cationic core-shell nanoparticles self-assembled from a biodegradable copolymer. Nat. Mater., 5(10):791-796.

[23]Yamanaka, T., Matsumoto, S., Teramukai, S., Ishiwata, R., Nagai, Y., Fukushima, M., 2007a. Analysis of risk factors for severe adverse effects of oral 5-fluorouracil S-1 in patients with advanced gastric cancer. Gastric Cancer, 10(2):129-134.

[24]Yamanaka, T., Matsumoto, S., Teramukai, S., Ishiwata, R., Nagai, Y., Fukushima, M., 2007b. Predictive value of chemotherapy-induced neutropenia for the efficacy of oral fluoropyrimidine S-1 in advanced gastric carcinoma. Brit. J. Cancer, 97(1):37-42.

[25]Yamanaka, T., Matsumoto, S., Teramukai, S., Ishiwata, R., Nagai, Y., Fukushima, M., 2008. Safety evaluation of oral fluoropyrimidine S-1 for short- and long-term delivery in advanced gastric cancer: analysis of 3758 patients. Cancer Chemother. Pharmacol., 61(2):335-343.

[26]Yao, H., Ng, S.S., Tucker, W.O., Tsang, Y.K.T., Man, K., Wang, X.M., Chow, B.K., Kung, H.F., Tang, G.P., Lin, M.C., 2009. The gene transfection efficiency of a folate-PEI600-cyclodextrin nanopolymer. Biomaterials, 30(29):5793-5803.

[27]Zeng, Z., Wang, X., Zhang, Y., Liu, X., Zhou, W., Li, N., 2009. Preparation and characterization of tegafur magnetic thermosensitive liposomes. Pharmac. Devel. Technol., 14(4):350-357.

[28]Zhang, Y.X., Dai, G.F., Wang, L., Tao, J.C., 2007. Synthesis and cytotoxicity of novel fatty acid-nucleoside conjugates. Bioorg. Med. Chem. Lett., 17(6):1613-1615.

[29]Zhao, D.J., Lu, X., Jiang, Q.Y., Chen, D., Zhou, J., Yu, H., Wang, Q.Q., Tang, G.P., 2009. Preparation of floxuridine loaded polycation and its antitumor activity. J. Zhejiang Univ. (Med. Sci.), 38(1):53-58 (in Chinese).

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