The targeting effect of H7K(R2)2-modified pH-sensitive liposomes on U87-MG cells

doi:10.5246/jcps.2015.10.084

Journal of Chinese Pharmaceutical Sciences ›› 2015, Vol. 24 ›› Issue (10): 660-665.DOI: 10.5246/jcps.2015.10.084

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The targeting effect of H7K(R2)2-modified pH-sensitive liposomes on U87-MG cells

Yang Zhao¹, Wei Ren¹, Ting Zhong¹, Chao Wang¹, Weiqiang Zhang¹, Dan Huang¹, Shuang Zhang¹, Yang Guo¹, Xin Yao¹, Xuan Zhang^1*, Qiang Zhang^1,2

1. Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China
2. State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center, Beijing 100191, China

Received:2015-05-22 Revised:2015-06-22 Online:2015-10-21 Published:2015-07-12
Contact: Tel./Fax: 86-10-82805928, E-mail: xuanzhang@bjmu.edu.cn
Supported by:
Specialized Research Fund for the Doctoral Program of Higher Education (Grant No. 20120001110012) and the National Basic Research Program of China (973 Program, Grant No. 2013CB932501) and National Natural Science Foundation of China (Grant No. 81172992).

Abstract

Abstract:

The present study aimed to investigate the targeting effect of H₇K(R₂)₂-modified pH-sensitive liposomes on U87-MG cells. Using coumarin-6 as a fluorescence probe, we prepared H₇K(R₂)₂-modified pH-sensitive liposomes (designated as coumarin-6-PSL-H₇K(R₂)₂). The flow cytometry assay was used to evaluate the effect of H₇K(R₂)₂proportions on the cellular uptake and endocytosis pathways of coumarin-6-PSL-H₇K(R₂)₂ on U87-MG cells_.The circular dichroism (CD) spectroscopy assay was used to investigate the secondary structures of H₇K(R₂)₂ peptide at pH 7.4 and pH 6.8, respectively. Our results indicated that the 2.5% proportion of H₇K(R₂)₂ in the coumarin-6-PSL-H₇K(R₂)₂ was superior to those of 1% and 3.5% of H₇K(R₂)₂. The uptake of coumarin-6-PSL-H₇K(R₂)₂ on U87-MG cells was not inhibited by filipin, M-β-CD or chlorpromazine. The secondary structure of H₇K(R₂)₂at pH 6.8 was mostly presented as β-turn. In conclusion, we suggested that the appropriate proportion of H₇K(R₂)₂ in the H₇K(R₂)₂-modified pH-sensitive liposomes could be set at 2.5%. The cellular uptake pathway for H₇K(R₂)₂-modified pH-sensitive liposomes was via the cell penetrating capacity of H₇K(R₂)₂ which responded to acidic condition. The secondary structure of H₇K(R₂)₂at pH 6.8, which was presented as the shape of hairpin, might be mainly responsible for its targeting and cell penetrating effect.

Key words: H7K(R2)2-modified, pH-sensitive liposomes, Cellular uptake pathway, Secondary structure, U87-MG cells

CLC Number:

R945

Supporting:

Yang Zhao, Wei Ren, Ting Zhong, Chao Wang, Weiqiang Zhang, Dan Huang, Shuang Zhang, Yang Guo, Xin Yao, Xuan Zhang, Qiang Zhang. The targeting effect of H7K(R2)2-modified pH-sensitive liposomes on U87-MG cells[J]. Journal of Chinese Pharmaceutical Sciences, 2015, 24(10): 660-665.

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The targeting effect of H7K(R2)2-modified pH-sensitive liposomes on U87-MG cells

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