Dimeric c(RGD) peptide conjugated nanostructured lipid carriers for efficient delivery of Gambogic acid to breast cancer

Dereje Kebebe,1–3,* Yumei Wu,1,2,* Bing Zhang,1,2 Jian Yang,1,2 Yuanyuan Liu,1,2 Xinyue Li,1,2 Zhe Ma,1,2 Peng Lu,1,2 Zhidong Liu,1,2 Jiawei Li1,21Tianjin State Key Laboratory of Modern Chinese Medicine, Institute of Traditional Chinese Medicine, Tianjin University of Traditional...

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Autores principales:	Kebebe D, Wu Y, Zhang B, Yang J, Liu Y, Li X, Ma Z, Lu P, Liu Z, Li J
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2019
Materias:	c(RGD) peptides Nanostructured Lipid Carriers Gambogic acid Breast cancer Cell uptake Antitumor Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/fa8b903cb59146a1af25c798a97ec34c
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spelling	oai:doaj.org-article:fa8b903cb59146a1af25c798a97ec34c2021-12-02T08:57:16ZDimeric c(RGD) peptide conjugated nanostructured lipid carriers for efficient delivery of Gambogic acid to breast cancer1178-2013https://doaj.org/article/fa8b903cb59146a1af25c798a97ec34c2019-08-01T00:00:00Zhttps://www.dovepress.com/dimeric-crgd-peptide-conjugated-nanostructured-lipid-carriers-for-effi-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Dereje Kebebe,1–3,* Yumei Wu,1,2,* Bing Zhang,1,2 Jian Yang,1,2 Yuanyuan Liu,1,2 Xinyue Li,1,2 Zhe Ma,1,2 Peng Lu,1,2 Zhidong Liu,1,2 Jiawei Li1,21Tianjin State Key Laboratory of Modern Chinese Medicine, Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, People’s Republic of China; 2Engineering Research Center of Modern Chinese Medicine Discovery and Preparation Technique, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, People’s Republic of China; 3Department of Pharmaceutics, School of Pharmacy, Institute of Health Sciences, Jimma University, Jimma, Ethiopia*These authors contributed equally to this workBackground and purpose: Gambogic acid (GA) is a natural compound that exhibited a promising multi-target antitumor activity against several types of cancer. However, the clinical application of this drug is limited due to its poor solubility and low tumor cell-specific delivery. In this study, the monomeric and dimeric Cyclo (Arg-Gly-Asp) c(RGD) tumor targeting peptides (c(RGDfK) and E-[c(RGDfK)2]) were used to modify GA loaded nanostructured lipid carriers (NLC) to reduce the limitations associated with GA and improve its antitumor activity.Methods: GA-NLC was prepared by emulsification and solvent evaporation methods and the surface of the NLC was conjugated with the c(RGD) peptides via an amide bond. The formulations were characterized for particle size, morphology and zeta potential, encapsulation efficiency and drug loading. The in-vitro cytotoxicity and cell uptake studies were conducted using 4T1 cell. Furthermore, the in-vivo antitumor activity and bio-distribution study were performed on female BALB/c nude mice.Results: The c(RGD) peptides modified GA-NLC was successfully prepared with the particles size about 20 nm. The HPLC analysis, FT-IR and 1H-NMR spectra confirmed the successful conjugation of the peptides with the NLC. The in-vitro cytotoxicity study on 4T1 cells revealed that c(RGD) peptides modified GA-NLCs showed significantly higher cytotoxicity at 0.25 and 0.5 μg/mL as compared to unmodified GA-NLC. Furthermore, the cell uptake study demonstrated that better accumulation of E-[c(RGDfK)2] peptides modified NLC in 4T1 cell after 12 h incubation. Moreover, the in-vivo study showed that c(RGD)s functionalized GA-NLC exhibited better accumulation in tumor tissue and tumor growth inhibition. In contrast to the monomeric c(RGD) peptide, the dimeric c(RGD) peptide (E-[c(RGDfK)2]) conjugated GA-NLC showed the improved antitumor activity and tumor targeting ability of GA-NLC.Conclusion: These data provide further support for the potential clinical applications of E-[c(RGDfK)2]-GA-NLC in breast cancer therapy.Keywords: c(RGD) peptides, nanostructured lipid carriers, Gambogic acid, breast cancer, cell uptake, antitumorKebebe DWu YZhang BYang JLiu YLi XMa ZLu PLiu ZLi JDove Medical Pressarticlec(RGD) peptidesNanostructured Lipid CarriersGambogic acidBreast cancerCell uptakeAntitumorMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 14, Pp 6179-6195 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	c(RGD) peptides Nanostructured Lipid Carriers Gambogic acid Breast cancer Cell uptake Antitumor Medicine (General) R5-920
spellingShingle	c(RGD) peptides Nanostructured Lipid Carriers Gambogic acid Breast cancer Cell uptake Antitumor Medicine (General) R5-920 Kebebe D Wu Y Zhang B Yang J Liu Y Li X Ma Z Lu P Liu Z Li J Dimeric c(RGD) peptide conjugated nanostructured lipid carriers for efficient delivery of Gambogic acid to breast cancer
description	Dereje Kebebe,1–3,* Yumei Wu,1,2,* Bing Zhang,1,2 Jian Yang,1,2 Yuanyuan Liu,1,2 Xinyue Li,1,2 Zhe Ma,1,2 Peng Lu,1,2 Zhidong Liu,1,2 Jiawei Li1,21Tianjin State Key Laboratory of Modern Chinese Medicine, Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, People’s Republic of China; 2Engineering Research Center of Modern Chinese Medicine Discovery and Preparation Technique, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, People’s Republic of China; 3Department of Pharmaceutics, School of Pharmacy, Institute of Health Sciences, Jimma University, Jimma, Ethiopia*These authors contributed equally to this workBackground and purpose: Gambogic acid (GA) is a natural compound that exhibited a promising multi-target antitumor activity against several types of cancer. However, the clinical application of this drug is limited due to its poor solubility and low tumor cell-specific delivery. In this study, the monomeric and dimeric Cyclo (Arg-Gly-Asp) c(RGD) tumor targeting peptides (c(RGDfK) and E-[c(RGDfK)2]) were used to modify GA loaded nanostructured lipid carriers (NLC) to reduce the limitations associated with GA and improve its antitumor activity.Methods: GA-NLC was prepared by emulsification and solvent evaporation methods and the surface of the NLC was conjugated with the c(RGD) peptides via an amide bond. The formulations were characterized for particle size, morphology and zeta potential, encapsulation efficiency and drug loading. The in-vitro cytotoxicity and cell uptake studies were conducted using 4T1 cell. Furthermore, the in-vivo antitumor activity and bio-distribution study were performed on female BALB/c nude mice.Results: The c(RGD) peptides modified GA-NLC was successfully prepared with the particles size about 20 nm. The HPLC analysis, FT-IR and 1H-NMR spectra confirmed the successful conjugation of the peptides with the NLC. The in-vitro cytotoxicity study on 4T1 cells revealed that c(RGD) peptides modified GA-NLCs showed significantly higher cytotoxicity at 0.25 and 0.5 μg/mL as compared to unmodified GA-NLC. Furthermore, the cell uptake study demonstrated that better accumulation of E-[c(RGDfK)2] peptides modified NLC in 4T1 cell after 12 h incubation. Moreover, the in-vivo study showed that c(RGD)s functionalized GA-NLC exhibited better accumulation in tumor tissue and tumor growth inhibition. In contrast to the monomeric c(RGD) peptide, the dimeric c(RGD) peptide (E-[c(RGDfK)2]) conjugated GA-NLC showed the improved antitumor activity and tumor targeting ability of GA-NLC.Conclusion: These data provide further support for the potential clinical applications of E-[c(RGDfK)2]-GA-NLC in breast cancer therapy.Keywords: c(RGD) peptides, nanostructured lipid carriers, Gambogic acid, breast cancer, cell uptake, antitumor
format	article
author	Kebebe D Wu Y Zhang B Yang J Liu Y Li X Ma Z Lu P Liu Z Li J
author_facet	Kebebe D Wu Y Zhang B Yang J Liu Y Li X Ma Z Lu P Liu Z Li J
author_sort	Kebebe D
title	Dimeric c(RGD) peptide conjugated nanostructured lipid carriers for efficient delivery of Gambogic acid to breast cancer
title_short	Dimeric c(RGD) peptide conjugated nanostructured lipid carriers for efficient delivery of Gambogic acid to breast cancer
title_full	Dimeric c(RGD) peptide conjugated nanostructured lipid carriers for efficient delivery of Gambogic acid to breast cancer
title_fullStr	Dimeric c(RGD) peptide conjugated nanostructured lipid carriers for efficient delivery of Gambogic acid to breast cancer
title_full_unstemmed	Dimeric c(RGD) peptide conjugated nanostructured lipid carriers for efficient delivery of Gambogic acid to breast cancer
title_sort	dimeric c(rgd) peptide conjugated nanostructured lipid carriers for efficient delivery of gambogic acid to breast cancer
publisher	Dove Medical Press
publishDate	2019
url	https://doaj.org/article/fa8b903cb59146a1af25c798a97ec34c
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Dimeric c(RGD) peptide conjugated nanostructured lipid carriers for efficient delivery of Gambogic acid to breast cancer

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