Self-assembled micelles of amphiphilic poly(L-phenylalanine)-b-poly(L-serine) polypeptides for tumor-targeted delivery

Ziming Zhao,1,2,* Yu Wang,1,2,* Jin Han,1,2 Keli Wang,1 Dan Yang,1,2 Yihua Yang,1,2 Qian Du,1,2 Yuanjian Song,3 Xiaoxing Yin1,2 1Department of Pharmacy, 2Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, 3Department of Basic Medical Sciences, Xuzhou Medical College, Xuzhou, People...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Zhao ZM, Wang Y, Han J, Wang KL, Yang D, Yang YH, Du Q, Song YJ, Yin XX
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2014
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/416c8c5ffdb348eeb9d84c7b04452419
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:416c8c5ffdb348eeb9d84c7b04452419
record_format	dspace
spelling	oai:doaj.org-article:416c8c5ffdb348eeb9d84c7b044524192021-12-02T06:34:19ZSelf-assembled micelles of amphiphilic poly(L-phenylalanine)-b-poly(L-serine) polypeptides for tumor-targeted delivery1178-2013https://doaj.org/article/416c8c5ffdb348eeb9d84c7b044524192014-12-01T00:00:00Zhttp://www.dovepress.com/self-assembled-micelles-of-amphiphilic-polyl-phenylalanine-b-polyl-ser-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013 Ziming Zhao,1,2,* Yu Wang,1,2,* Jin Han,1,2 Keli Wang,1 Dan Yang,1,2 Yihua Yang,1,2 Qian Du,1,2 Yuanjian Song,3 Xiaoxing Yin1,2 1Department of Pharmacy, 2Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, 3Department of Basic Medical Sciences, Xuzhou Medical College, Xuzhou, People’s Republic of China *These authors contributed equally to this work Abstract: The aim of this work was to design, synthesize, and characterize self-assembled micelles based on polypeptides as a potential antitumor drug carrier. Amphiphilic poly(L-phenylalanine)-b-poly(L-serine) (PFS) polypeptides were obtained through the polymerization of N-carboxyanhydride. As a novel hydrophilic segment, poly(L-serine) was utilized to enhance tumor targeting due to a large demand of tumors for serine. PFS could self-assemble into micelles with an average diameter of 110–240 nm and a slightly negative charge. PFS polypeptides adopted random coil in pH 7.4 phosphate-buffered saline and could partly transform to a-helix induced by trifluoroethanol. PFS micelles with a low critical micelle concentration of 4.0 µg mL-1 were stable in pH 5–9 buffers and serum albumin solution. PFS micelles had a loading capacity of 3.8% for coumarin-6 and exhibited a sustained drug release. Coumarin-6 loaded rhodamine B isothiocyanate-labeled PFS micelles were incubated with Huh-7 tumor cells to study the correlation between drugs and carriers during endocytosis. The uptake of drugs was consistent with the micelles, illustrating that the intracellular transport of drugs highly depended on the micelles. PFS micelles diffused in whole cytoplasm while coumarin-6 assumed localized distribution, suggesting that the micelles could release the loaded drugs in particular areas. The internalization mechanism of PFS micelles was involved with clathrin-mediated endocytosis and macropinocytosis. Excess serine inhibited the uptake of PFS micelles, which demonstrated that serine receptors played a positive role in the internalization of PFS. The more interesting thing was that the uptake inhibition impacted on normal cells but not on tumor cells at the physiological concentration of serine. The difference in the uptake of PFS micelles was fourfold as high between the tumor cells and the normal cells, which indicated that PFS micelles had good tumor targeting in vitro. In conclusion, PFS micelles reported in this work were a promising drug delivery system for tumor targeting therapy. Keywords: amphiphilic polypeptides, micelles, poly(L-serine), poly(L-phenylalanine), tumor therapy Zhao ZMWang YHan JWang KLYang DYang YHDu QSong YJYin XXDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2014, Iss Issue 1, Pp 5849-5862 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Zhao ZM Wang Y Han J Wang KL Yang D Yang YH Du Q Song YJ Yin XX Self-assembled micelles of amphiphilic poly(L-phenylalanine)-b-poly(L-serine) polypeptides for tumor-targeted delivery
description	Ziming Zhao,1,2,* Yu Wang,1,2,* Jin Han,1,2 Keli Wang,1 Dan Yang,1,2 Yihua Yang,1,2 Qian Du,1,2 Yuanjian Song,3 Xiaoxing Yin1,2 1Department of Pharmacy, 2Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, 3Department of Basic Medical Sciences, Xuzhou Medical College, Xuzhou, People’s Republic of China *These authors contributed equally to this work Abstract: The aim of this work was to design, synthesize, and characterize self-assembled micelles based on polypeptides as a potential antitumor drug carrier. Amphiphilic poly(L-phenylalanine)-b-poly(L-serine) (PFS) polypeptides were obtained through the polymerization of N-carboxyanhydride. As a novel hydrophilic segment, poly(L-serine) was utilized to enhance tumor targeting due to a large demand of tumors for serine. PFS could self-assemble into micelles with an average diameter of 110–240 nm and a slightly negative charge. PFS polypeptides adopted random coil in pH 7.4 phosphate-buffered saline and could partly transform to a-helix induced by trifluoroethanol. PFS micelles with a low critical micelle concentration of 4.0 µg mL-1 were stable in pH 5–9 buffers and serum albumin solution. PFS micelles had a loading capacity of 3.8% for coumarin-6 and exhibited a sustained drug release. Coumarin-6 loaded rhodamine B isothiocyanate-labeled PFS micelles were incubated with Huh-7 tumor cells to study the correlation between drugs and carriers during endocytosis. The uptake of drugs was consistent with the micelles, illustrating that the intracellular transport of drugs highly depended on the micelles. PFS micelles diffused in whole cytoplasm while coumarin-6 assumed localized distribution, suggesting that the micelles could release the loaded drugs in particular areas. The internalization mechanism of PFS micelles was involved with clathrin-mediated endocytosis and macropinocytosis. Excess serine inhibited the uptake of PFS micelles, which demonstrated that serine receptors played a positive role in the internalization of PFS. The more interesting thing was that the uptake inhibition impacted on normal cells but not on tumor cells at the physiological concentration of serine. The difference in the uptake of PFS micelles was fourfold as high between the tumor cells and the normal cells, which indicated that PFS micelles had good tumor targeting in vitro. In conclusion, PFS micelles reported in this work were a promising drug delivery system for tumor targeting therapy. Keywords: amphiphilic polypeptides, micelles, poly(L-serine), poly(L-phenylalanine), tumor therapy
format	article
author	Zhao ZM Wang Y Han J Wang KL Yang D Yang YH Du Q Song YJ Yin XX
author_facet	Zhao ZM Wang Y Han J Wang KL Yang D Yang YH Du Q Song YJ Yin XX
author_sort	Zhao ZM
title	Self-assembled micelles of amphiphilic poly(L-phenylalanine)-b-poly(L-serine) polypeptides for tumor-targeted delivery
title_short	Self-assembled micelles of amphiphilic poly(L-phenylalanine)-b-poly(L-serine) polypeptides for tumor-targeted delivery
title_full	Self-assembled micelles of amphiphilic poly(L-phenylalanine)-b-poly(L-serine) polypeptides for tumor-targeted delivery
title_fullStr	Self-assembled micelles of amphiphilic poly(L-phenylalanine)-b-poly(L-serine) polypeptides for tumor-targeted delivery
title_full_unstemmed	Self-assembled micelles of amphiphilic poly(L-phenylalanine)-b-poly(L-serine) polypeptides for tumor-targeted delivery
title_sort	self-assembled micelles of amphiphilic poly(l-phenylalanine)-b-poly(l-serine) polypeptides for tumor-targeted delivery
publisher	Dove Medical Press
publishDate	2014
url	https://doaj.org/article/416c8c5ffdb348eeb9d84c7b04452419
work_keys_str_mv	AT zhaozm selfassembledmicellesofamphiphilicpolylphenylalaninebpolylserinepolypeptidesfortumortargeteddelivery AT wangy selfassembledmicellesofamphiphilicpolylphenylalaninebpolylserinepolypeptidesfortumortargeteddelivery AT hanj selfassembledmicellesofamphiphilicpolylphenylalaninebpolylserinepolypeptidesfortumortargeteddelivery AT wangkl selfassembledmicellesofamphiphilicpolylphenylalaninebpolylserinepolypeptidesfortumortargeteddelivery AT yangd selfassembledmicellesofamphiphilicpolylphenylalaninebpolylserinepolypeptidesfortumortargeteddelivery AT yangyh selfassembledmicellesofamphiphilicpolylphenylalaninebpolylserinepolypeptidesfortumortargeteddelivery AT duq selfassembledmicellesofamphiphilicpolylphenylalaninebpolylserinepolypeptidesfortumortargeteddelivery AT songyj selfassembledmicellesofamphiphilicpolylphenylalaninebpolylserinepolypeptidesfortumortargeteddelivery AT yinxx selfassembledmicellesofamphiphilicpolylphenylalaninebpolylserinepolypeptidesfortumortargeteddelivery
_version_	1718399809247772672

Self-assembled micelles of amphiphilic poly(L-phenylalanine)-b-poly(L-serine) polypeptides for tumor-targeted delivery

Ejemplares similares