Research Articles

Construction of cationic amphipathic peptide-lipid nanoparticle and evaluation of its cytotoxicity and stability in vitro

Expand
  • 1. School of Life Sciences, Shanghai University, Shanghai 200444, China
    2. Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences,Suzhou 215123, Jiangsu, China

Received date: 2016-03-16

  Online published: 2018-03-05

Abstract

In this paper, cationic amphipathic R peptide (RLARLLRRLARWLR) was chosen to construct peptide-lipid nanoparticle. Recombination and interaction of R peptide with lipid mixture were studied using lipid emulsion clearance assay and blue shift of tryptophan fluorescence assay. The diameter and surface characterization of cationic amphipathic R peptide-lipid nanoparticle (R-LNP) were obtained with transmission electron microscope (TEM), dynamic light scattering (DLS) and zeta potential measurements. MTT assay was used to investigate cytotoxicity of R-LNP. Stability of R-LNP and R peptide against chymotrypsin and trypsin was explored using ultra high performance liquid chromatography (UPLC). The results showed that R peptide caused reconstruction of lipid to form lipid nanoparticle with a diameter of (14.7$\pm $0.1) nm and zeta potential of 17.8 mV. Hydrophobic amino acids of R peptide inserted in the hydrophobic core of lipid nanoparticle. Cytotoxicity of R peptide was retained in R-LNP, of which half-inhibitory concentration for A549 and MCF-7 was (5.93$\pm $0.75) $\mu$mol/L and (4.36$\pm $0.40) $\mu$mol/L respectively. UPLC results showed that R-LNP increased stability of R peptide, facilitating its translational application in vivo.

Cite this article

WANG Qiao, FEI Hao . Construction of cationic amphipathic peptide-lipid nanoparticle and evaluation of its cytotoxicity and stability in vitro[J]. Journal of Shanghai University, 2018 , 24(1) : 142 -150 . DOI: DOi:10.12066/j.issn.1007-2861.1758

References

[1] Gogonea V . Structural insights into high density lipoprotein: old models and new facts[J]. Front Pharmacol, 2015, DOI: 10.3389/fphar.2015.00318.
[2] 王若宁, 刘聪燕, 周建平 , 等. 脂蛋白纳米药物传输系统研究进展[J]. 中国药科大学学报, 2014,45(1):10-16.
[3] Huang H, Cruz W, Chen J , et al. Learning from biology: synthetic lipoproteins for drug delivery[J]. Wires Nanomed Nanobi, 2015,7(3):298-314.
[4] Brouillette C G, Anantharamaiah G M . Structural models of human apolipoprotein A-I[J]. Biochimica et Biophysica Acta, 1995,1256(2):103-129.
[5] Chung B H, Anatharamaiah G M, Brouillette C G , et al. Studies of synthetic peptide analogs of the amphipathic helix. Correlation of structure with function[J]. J Biol Chem, 1985,260(18):10256-10262.
[6] Datta G, Chaddha M, Hama S , et al. Effects of increasing hydrophobicity on the physical-chemical and biological properties of a class A amphipathic helical peptide[J]. J Lipid Res, 2001,42(7):1096-1104.
[7] Garber D W, Handattu S P, Datta G , et al. Atherosclerosis and vascular disease: effects of peptide mimetics of apolipoproteins[J]. Curr Pharm Biotechnol, 2006,7(4):235-240.
[8] Mishra V K, Palgunachari M N, Segrest J P , et al. Interactions of synthetic peptide analogs of the class A amphipathic helix with lipids: evidence for the snorkel hypojournal[J]. J Biol Chem, 1994,269(10):7185-7191.
[9] Wang Q, Ma X, Fei H , et al. A peptide-lipid nanoparticle assembly platform with integrated functions for targeted cell delivery[J]. J Mater Chem B, 2016,4(8):1535-1543.
[10] Mader J S, Hoskin D W . Cationic antimicrobial peptides as novel cytotoxic agents for cancer treatment[J]. Expert Opin Inv Drug, 2006,15(8):933-946.
[11] Gaspar D, Veiga A S, Castanho M A R B. From antimicrobial to anticancer peptides. A review[J]. Front Microbiol, 2013,4:1-16.
[12] Leuschner C, Hansel W . Membrane disrupting lytic peptides for cancer treatments[J]. Curr Pharm Design, 2004,10(19):2299-2310.
[13] 潘广瑞, 赵晖 . 抗菌肽在肿瘤方面的研究进展[J]. 医学综述, 2015,21(18):3318-3320.
[14] Mishra V K, Palgunachari M N . Interaction of model class A1, class A2, and class Y amphipathic helical peptides with membranes[J]. Biochemistry, 1996,35(34):11210-11220.
[15] 王克全, 徐寒梅 . 多肽类药物的研究进展[J]. 药学进展, 2015,39(9):642-650.
[16] Luo H M, Lu L S, Yang F , et al. Nasopharyngeal cancer-specific therapy based on fusion peptide-functionalized lipid nanoparticles[J]. ACS Nano, 2014,8(5):4334-4347.
[17] Huang C, Jin H L, Qian Y , et al. Hybrid melittin cytolytic peptide-driven ultrasmall lipid nanoparticles block melanoma growth in vivo[J]. ACS Nano, 2013,7(7):5791-5800.
[18] Ashaben P, Kishore C, Mitra A K . Recent developments in protein and peptide parenteral delivery approaches[J]. Ther Deliv, 2014,5(3):337-365.
Outlines

/