Folic acid-tethered Pep-1 peptide-conjugated liposomal nanocarrier for enhanced intracellular drug delivery to cancer cells: conformational characterization and in vitro cellular uptake evaluation

Myung Joo Kang, Sang Han Park, Mean Hyung Kang, Min Jung Park, Young Wook Choi College of Pharmacy, Chung-Ang University, Seoul, Korea Background: A novel dual ligand&ndash;modified liposome, folic acid-tethered Pep-1 peptide-conjugated liposomal nanocarrier (FP-Lipo), was designed to overco...

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Autores principales:	Kang MJ, Park SH, Kang MH, Park MJ, Choi YW
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2013
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/752e3a754477473f86610c44a0a32c05
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spelling	oai:doaj.org-article:752e3a754477473f86610c44a0a32c052021-12-02T00:40:16ZFolic acid-tethered Pep-1 peptide-conjugated liposomal nanocarrier for enhanced intracellular drug delivery to cancer cells: conformational characterization and in vitro cellular uptake evaluation1176-91141178-2013https://doaj.org/article/752e3a754477473f86610c44a0a32c052013-03-01T00:00:00Zhttp://www.dovepress.com/folic-acid-tethered-pep-1-peptide-conjugated-liposomal-nanocarrier-for-a12478https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Myung Joo Kang, Sang Han Park, Mean Hyung Kang, Min Jung Park, Young Wook Choi College of Pharmacy, Chung-Ang University, Seoul, Korea Background: A novel dual ligand&ndash;modified liposome, folic acid-tethered Pep-1 peptide-conjugated liposomal nanocarrier (FP-Lipo), was designed to overcome the nonselectivity of conventional penetrating peptide-tagged nanoparticulates and to provide the advantage of selective targeting of the folic acid receptor, which is frequently overexpressed on epithelial cancer cells. Methods: FP-Lipo was prepared by a sequential process of formation of a maleimide-derivatized small unilamellar vesicle, postinsertion of distearoyl phosphatidyl ethanolamine-polyethylene glycol 2000&ndash;folate to the vesicle, and Pep-1 peptide conjugation via thiol-maleimide linkage. Conformational and physical characteristics of the FP-Lipo nanocarriers were investigated for the extent of Pep-1 peptide and folic acid on the surface, vesicle size, and zeta potential. In vitro cellular uptake behaviors of the novel carrier containing a fluorescein dextran isothiocyanate probe were examined by spectrophotometry or by confocal laser scanning microscopy. Results: A novel nanocarrier bearing approximately 750 folate ligands and 100 penetrating peptides per vesicle was successfully prepared. The physical properties were as follows: 140 nm in size; 5 mV in zeta potential; less than 0.3 in polydispersity index. An in vitro cellular uptake study revealed that the FP-Lipo nanocarrier system exhibited more than twofold enhanced translocation into the folic acid receptor&ndash;positive HeLa cells compared with the single Pep-1 peptide&ndash;modified liposome. Meanwhile, its cellular association and internalization into the folic acid receptor&ndash;negative normal HaCaT cells was comparable with that of Pep-1 peptide&ndash;modified liposome. Conclusion: An advanced dual ligand-modified liposome is potentially useful for the treatment of folic acid receptor&ndash;positive tumors with high translocation capability of the penetrating peptide&ndash;modified liposome. Keywords: liposome, folic acid, Pep-1 peptide, cell-penetrating peptide, intracellular delivery, targeted deliveryKang MJPark SHKang MHPark MJChoi YWDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2013, Iss default, Pp 1155-1165 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Kang MJ Park SH Kang MH Park MJ Choi YW Folic acid-tethered Pep-1 peptide-conjugated liposomal nanocarrier for enhanced intracellular drug delivery to cancer cells: conformational characterization and in vitro cellular uptake evaluation
description	Myung Joo Kang, Sang Han Park, Mean Hyung Kang, Min Jung Park, Young Wook Choi College of Pharmacy, Chung-Ang University, Seoul, Korea Background: A novel dual ligand&ndash;modified liposome, folic acid-tethered Pep-1 peptide-conjugated liposomal nanocarrier (FP-Lipo), was designed to overcome the nonselectivity of conventional penetrating peptide-tagged nanoparticulates and to provide the advantage of selective targeting of the folic acid receptor, which is frequently overexpressed on epithelial cancer cells. Methods: FP-Lipo was prepared by a sequential process of formation of a maleimide-derivatized small unilamellar vesicle, postinsertion of distearoyl phosphatidyl ethanolamine-polyethylene glycol 2000&ndash;folate to the vesicle, and Pep-1 peptide conjugation via thiol-maleimide linkage. Conformational and physical characteristics of the FP-Lipo nanocarriers were investigated for the extent of Pep-1 peptide and folic acid on the surface, vesicle size, and zeta potential. In vitro cellular uptake behaviors of the novel carrier containing a fluorescein dextran isothiocyanate probe were examined by spectrophotometry or by confocal laser scanning microscopy. Results: A novel nanocarrier bearing approximately 750 folate ligands and 100 penetrating peptides per vesicle was successfully prepared. The physical properties were as follows: 140 nm in size; 5 mV in zeta potential; less than 0.3 in polydispersity index. An in vitro cellular uptake study revealed that the FP-Lipo nanocarrier system exhibited more than twofold enhanced translocation into the folic acid receptor&ndash;positive HeLa cells compared with the single Pep-1 peptide&ndash;modified liposome. Meanwhile, its cellular association and internalization into the folic acid receptor&ndash;negative normal HaCaT cells was comparable with that of Pep-1 peptide&ndash;modified liposome. Conclusion: An advanced dual ligand-modified liposome is potentially useful for the treatment of folic acid receptor&ndash;positive tumors with high translocation capability of the penetrating peptide&ndash;modified liposome. Keywords: liposome, folic acid, Pep-1 peptide, cell-penetrating peptide, intracellular delivery, targeted delivery
format	article
author	Kang MJ Park SH Kang MH Park MJ Choi YW
author_facet	Kang MJ Park SH Kang MH Park MJ Choi YW
author_sort	Kang MJ
title	Folic acid-tethered Pep-1 peptide-conjugated liposomal nanocarrier for enhanced intracellular drug delivery to cancer cells: conformational characterization and in vitro cellular uptake evaluation
title_short	Folic acid-tethered Pep-1 peptide-conjugated liposomal nanocarrier for enhanced intracellular drug delivery to cancer cells: conformational characterization and in vitro cellular uptake evaluation
title_full	Folic acid-tethered Pep-1 peptide-conjugated liposomal nanocarrier for enhanced intracellular drug delivery to cancer cells: conformational characterization and in vitro cellular uptake evaluation
title_fullStr	Folic acid-tethered Pep-1 peptide-conjugated liposomal nanocarrier for enhanced intracellular drug delivery to cancer cells: conformational characterization and in vitro cellular uptake evaluation
title_full_unstemmed	Folic acid-tethered Pep-1 peptide-conjugated liposomal nanocarrier for enhanced intracellular drug delivery to cancer cells: conformational characterization and in vitro cellular uptake evaluation
title_sort	folic acid-tethered pep-1 peptide-conjugated liposomal nanocarrier for enhanced intracellular drug delivery to cancer cells: conformational characterization and in vitro cellular uptake evaluation
publisher	Dove Medical Press
publishDate	2013
url	https://doaj.org/article/752e3a754477473f86610c44a0a32c05
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Folic acid-tethered Pep-1 peptide-conjugated liposomal nanocarrier for enhanced intracellular drug delivery to cancer cells: conformational characterization and in vitro cellular uptake evaluation

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