叶酸及细胞穿膜肽修饰的纳米脂质载体穿透体外肿瘤球模型研究

doi:10.5246/jcps.2015.10.085

中国药学(英文版) ›› 2015, Vol. 24 ›› Issue (10): 666-672.DOI: 10.5246/jcps.2015.10.085

叶酸及细胞穿膜肽修饰的纳米脂质载体穿透体外肿瘤球模型研究

庄鸿蒙^1,2, 孟婷婷^1,2, 高玮², 袁兰³, 齐宪荣^1,2*

1. 北京大学医学部药学院分子药剂学和新释药系统北京重点实验室, 北京 100191
2. 北京大学医学部药学院药剂学系, 北京 100191
3. 北京大学医学部医学分析中心, 北京 100191

收稿日期:2012-06-13 修回日期:2012-07-25 出版日期:2015-10-21 发布日期:2012-08-13
通讯作者: Tel.: 86-10-82801708, E-mail: qixr@bjmu.edu.cn
基金资助:
National key Basic Research Program (Grant No. 2013CB932501), National Natural Science Foundation of China (Grant No. 81273454 and 81473156), Beijing National Science Foundation (Grant No. 7132113), and Doctoral Foundation of the Ministry of Education (Grant No. 20130001110055).

Folate and cell penetrating peptide modification effects on penetration behavior of nanostructured lipid carriers using multicellular tumor spheroids

Hongmeng Zhuang^1,2, Tingting Meng^1,2, Wei Gao², Lan Yuan³, Xianrong Qi^1,2*

1. Beijing Key Laboratory of Molecular Pharmaceutics and New drug delivery System, Peking University Health Science Center, Beijing 100191, China
2. Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China
3. Medical and Healthy Analytical Center, Peking University Health Science Center, Beijing 100191, China

Received:2012-06-13 Revised:2012-07-25 Online:2015-10-21 Published:2012-08-13
Contact: Tel.: 86-10-82801708, E-mail: qixr@bjmu.edu.cn
Supported by:
National key Basic Research Program (Grant No. 2013CB932501), National Natural Science Foundation of China (Grant No. 81273454 and 81473156), Beijing National Science Foundation (Grant No. 7132113), and Doctoral Foundation of the Ministry of Education (Grant No. 20130001110055).

摘要/Abstract

摘要：

纳米递药系统的表面修饰作用会对载体的穿透能力产生影响。本研究通过使用叶酸配体和细胞穿膜肽分别修饰的纳米脂质载体,在堆积法建立的肿瘤球模型上实时分析细胞靶向和细胞穿透作用对于纳米脂质载体的肿瘤穿透能力的影响。研究结果表明细胞穿透肽修饰的纳米脂质载体不论是从穿透深度还是强度上, 在穿透早期都具备更好的穿透肿瘤球能力。

关键词: 纳米脂质载体, 肿瘤球, 堆积法, 叶酸, 细胞穿膜肽

Abstract:

Surface modification may have important influences on the penetration behavior of nanoscale drug delivery system. In the present study, we mainly focused on whether cell targeting or cell penetration could affect penetration abilities of nanostructuredlipid carriers (NLC). Real-time penetration of folate- or cell penetrating peptide (CPP)-modified NLC was evaluated using a multicellular tumor spheroid (MTS) established by stacking culture method as an in vitro testing platform. The results suggested that CPP modification had a better penetration behavior both on penetration depth and intensity compared with folate-modified NLC at the early stage of penetration process.

Key words: Nanostructured lipid carriers, Multicellular tumor spheroids, Stacking method, Folate, Cell penetrating peptide

中图分类号:

R945

Supporting:

庄鸿蒙, 孟婷婷, 高玮, 袁兰, 齐宪荣. 叶酸及细胞穿膜肽修饰的纳米脂质载体穿透体外肿瘤球模型研究[J]. 中国药学(英文版), 2015, 24(10): 666-672.

Hongmeng Zhuang, Tingting Meng, Wei Gao, Lan Yuan, Xianrong Qi. Folate and cell penetrating peptide modification effects on penetration behavior of nanostructured lipid carriers using multicellular tumor spheroids[J]. Journal of Chinese Pharmaceutical Sciences, 2015, 24(10): 666-672.

参考文献

[1] Danhier, F.; Feron, O.; Preat, V. J. Control. Release. 2010, 148, 135-146.

[2] Xiang, B.; Dong, D.W.; Shi, N.Q.; Gao, W.; Yang, Z.Z.; Cui, Y.; Cao, D.Y.; Qi, X.R. Biomaterials. 2013, 34, 6976-6991.

[3] Cho, H.; Yoon, H.Y.; Koo, H.; Ko, S.; Shim, J.; Lee, J.; Kim, K.; Chan Kwon, I.; Kim, D. Biomaterials. 2011, 32, 7181-7190.

[4] Brannon-Peppas, L.; Blanchette, J.O. Adv. Drug Deliv. Rev. 2004, 56, 1649-1659.

[5] Gao, W.; Meng, T.T.; Shi, N.Q.; Zhuang, H.M.; Yang, Z.Z.; Qi, X.R. Adv. Healthcare Mater. 2015, 4, 748-759.

[6] Muller, R.H.; Radtke, M.; Wissing, S.A. Adv. Drug Deliv. Rev. 2002, 54, S131-155.

[7] Yang, Z.Z.; Li, J.Q.; Wang, A.A.; Dong, D.W.; Qi, X.R. Biomaterials. 2014, 35, 5226-5239.

[8] Mehta, G.; Hsiao, A.Y.; Ingram, M.; Luker, G.D.; Takayama, S. J. Control. Release. 2012, 164, 192-204.

[9] Laws, A. American Society for Cell Biology 49^th Annual Meeting 2009.

[10] Haycock, J.W.Methods Mol. Biol. 2011, 695, 1-15.

[11] Kunz-Schughart, L.A.; Freyer, J.P.; Hofstaedter, F.; Ebner, R. J. Biomol. Screen. 2004, 9, 273-285.

[12] Ingram, M.; Techy, G.B.; Saroufeem, R.; Yazan, O.; Narayan, K.S.; Goodwin, T.J.; Spaulding, G.F. In Vitro Cell Dev. Biol. Anim. 1997, 33, 459-466.

[13] Hirschhaeuser, F.; Menne, H.; Dittfeld, C.; West, J.; Mueller-Klieser, W.; Kunz-Schughart, L.A. J. Biotechnol. 2010, 148, 3-15.

[14] Torisawa, Y.S.; Takagi, A.; Shiku, H.; Yasukawa, T.; Matsue, T. Oncol. Rep. 2005, 13, 1107-1112.

[15] Bartosh, T.J.; Ylostalo, J.H.; Mohammadipoor, A.; Bazhanov, N.; Coble, K.; Claypool, K.; Lee, R.H.; Choi, H.; Prockop, D.J. Proc. Natl. Acad. Sci. USA. 2010, 107, 13724-13729.

[16] Liang, D.S.; Su, H.T.; Liu, Y.J.; Wang, A.T.; Qi, X.R. Biomaterials. 2015, 71, 11-23.

[17] Del, D.D.; Werbowetski, T.; Del, M.R. J. Neurooncol. 2004, 67, 295-303.

[18] Leamon, C. Adv. Drug Deliver. Rev. 2004, 56, 1127-1141.

[19] Wender, P.A.; Mitchell, D.J.; Pattabiraman, K.; Pelkey, E.T.; Steinman, L.; Rothbard, J.B. Proc. Natl. Acad. Sci. USA. 2000, 97, 13003-13008.

[20] Gao, W.; Xiang, B.; Meng, T.; Liu, F.; Qi, X. Biomaterials. 2013, 34, 4137-4149.

[21] Meng, T.; Li, J.; Qi, X.R. J. Chin. Pharm. Sci. 2014, 23, 145-152.

[22] Jain, A.; Shah, S.G.; Chugh, A. Pharm. Res. 2015, 32, 1920-1930.

[23] Ruczynski, J.; Wierzbicki, P.M.; Kogut-Wierzbicka, M.; Mucha, P.; Siedlecka-Kroplewska, K.; Rekowski, P. Folia Histochem. Cytobiol. 2014, 52, 257-269.

[24] Di Pisa, M.; Chassaing, G.; Swiecicki, J.M. Biochemistry-US. 2015, 54, 194-207.

[25] Sun, S.; Zhou, C.; Chen, S.; Liu, J.; Yu, J.; Chilek, J.; Zhao, L.; Yu, M.; Vinluan, R.; Huang, B.; Zheng, J. Bioconjugate Chem. 2014, 25, 453-459.

[26] Lelu, S.; Strand, S.P.; Steine, J.; Davies, C.L. Biomacromolecules. 2011, 12, 3656-3665.

[27] Dong, D.; Gao, W.; Liu, Y.; Qi, X.R. Cancer Lett. 2015, 359, 178-186.

[28] Mikhail, A.S.; Eetezadi, S.; Ekdawi, S.N.; Stewart, J.; Allen, C. Int. J. Pharm. 2014, 464, 168-177.

[29] Lu, Y.; Low, P.S. Adv. Drug Deliv. Rev. 2002, 54, 675-693.

[30] Weitman, S.D.; Lark, R.H.; Coney, L.R.; Fort, D.W.; Frasca, V.; Zurawski, V.J.; Kamen, B.A. Cancer Res. 1992, 52, 3396-3401.

叶酸及细胞穿膜肽修饰的纳米脂质载体穿透体外肿瘤球模型研究

Folate and cell penetrating peptide modification effects on penetration behavior of nanostructured lipid carriers using multicellular tumor spheroids

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