Heterogeneous dimer peptide-conjugated polylysine dendrimer-Fe3O4 composite as a novel nanoscale molecular probe for early diagnosis and therapy in hepatocellular carcinoma

Jian-Min Shen,1 Xin-Xin Li,1 Lin-Lan Fan,2 Xing Zhou,3 Ji-Min Han,1 Ming-Kang Jia,1 Liang-Fan Wu,1 Xiao-Xue Zhang,1 Jing Chen1 1School of Life Sciences, 2School of Basic Medical Sciences, Lanzhou University, 3The People’s Hospital of Gansu Province, Lanzhou, Gansu, China Abstract: A nove...

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Autores principales:	Shen JM, Li XX, Fan LL, Zhou X, Han JM, Jia MK, Wu LF, Zhang XX, Chen J
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2017
Materias:	Heterogeneous dimer peptide (HDP) Molecular probe Magnetic nanoparticles (MNPs) Targeting Hepatocellular carcinoma (HCC) Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/96d16e45c06a4ce786b184009df4120d
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spelling	oai:doaj.org-article:96d16e45c06a4ce786b184009df4120d2021-12-02T05:10:41ZHeterogeneous dimer peptide-conjugated polylysine dendrimer-Fe3O4 composite as a novel nanoscale molecular probe for early diagnosis and therapy in hepatocellular carcinoma1178-2013https://doaj.org/article/96d16e45c06a4ce786b184009df4120d2017-02-01T00:00:00Zhttps://www.dovepress.com/heterogeneous--dimer-peptide-conjugated-polylysine-dendrimer-fe3o4-com-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Jian-Min Shen,1 Xin-Xin Li,1 Lin-Lan Fan,2 Xing Zhou,3 Ji-Min Han,1 Ming-Kang Jia,1 Liang-Fan Wu,1 Xiao-Xue Zhang,1 Jing Chen1 1School of Life Sciences, 2School of Basic Medical Sciences, Lanzhou University, 3The People’s Hospital of Gansu Province, Lanzhou, Gansu, China Abstract: A novel nanoscale molecular probe is formulated in order to reduce toxicity and side effects of antitumor drug doxorubicin (DOX) in normal tissues and to enhance the detection sensitivity during early imaging diagnosis. The mechanism involves a specific targeting of Arg-Gly-Asp peptide (RGD)-GX1 heterogeneous dimer peptide-conjugated dendrigraft poly-l-lysine (DGL)–magnetic nanoparticle (MNP) composite by αvβ3-integrin/vasculature endothelium receptor-mediated synergetic effect. The physicochemical properties of the nanoprobe were characterized by using transmission electron microscope, Fourier transform infrared spectroscopy, X-ray diffraction, dynamic light scattering (DLS), and vibrating sample magnetometer. The average diameter of the resulting MNP–DGL–RGD-GX1–DOX nanoparticles (NPs) was ~150-160 nm by DLS under simulate physiological medium. In the present experimental system, the loading amount of DOX on NPs accounted for 414.4 mg/g for MNP–DGL–RGD-GX1–DOX. The results of cytotoxicity, flow cytometry, and cellular uptake consistently indicated that the MNP–DGL–RGD-GX1–DOX NPs were inclined to target HepG2 cells in selected three kinds of cells. In vitro exploration of molecular mechanism revealed that cell apoptosis was associated with the overexpression of Fas protein and the significant activation of caspase-3. In vivo magnetic resonance imaging and biodistribution study showed that the MNP–DGL–RGD-GX1–DOX formulation had high affinity to the tumor tissue, leading to more aggregation of NPs in the tumor. In vivo antitumor efficacy research verified that MNP–DGL–RGD-GX1–DOX NPs possessed significant antitumor activity and the tumor inhibitory rate reached 78.5%. These results suggested that NPs could be promising in application to early diagnosis and therapy in hepatocellular carcinoma as a specific nanoprobe. Keywords: heterogeneous dimer peptide (HDP), molecular probe, magnetic nanoparticles (MNPs), targeting, hepatocellular carcinoma (HCC)Shen JMLi XXFan LLZhou XHan JMJia MKWu LFZhang XXChen JDove Medical PressarticleHeterogeneous dimer peptide (HDP)Molecular probeMagnetic nanoparticles (MNPs)TargetingHepatocellular carcinoma (HCC)Medicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 12, Pp 1183-1200 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Heterogeneous dimer peptide (HDP) Molecular probe Magnetic nanoparticles (MNPs) Targeting Hepatocellular carcinoma (HCC) Medicine (General) R5-920
spellingShingle	Heterogeneous dimer peptide (HDP) Molecular probe Magnetic nanoparticles (MNPs) Targeting Hepatocellular carcinoma (HCC) Medicine (General) R5-920 Shen JM Li XX Fan LL Zhou X Han JM Jia MK Wu LF Zhang XX Chen J Heterogeneous dimer peptide-conjugated polylysine dendrimer-Fe3O4 composite as a novel nanoscale molecular probe for early diagnosis and therapy in hepatocellular carcinoma
description	Jian-Min Shen,1 Xin-Xin Li,1 Lin-Lan Fan,2 Xing Zhou,3 Ji-Min Han,1 Ming-Kang Jia,1 Liang-Fan Wu,1 Xiao-Xue Zhang,1 Jing Chen1 1School of Life Sciences, 2School of Basic Medical Sciences, Lanzhou University, 3The People’s Hospital of Gansu Province, Lanzhou, Gansu, China Abstract: A novel nanoscale molecular probe is formulated in order to reduce toxicity and side effects of antitumor drug doxorubicin (DOX) in normal tissues and to enhance the detection sensitivity during early imaging diagnosis. The mechanism involves a specific targeting of Arg-Gly-Asp peptide (RGD)-GX1 heterogeneous dimer peptide-conjugated dendrigraft poly-l-lysine (DGL)–magnetic nanoparticle (MNP) composite by αvβ3-integrin/vasculature endothelium receptor-mediated synergetic effect. The physicochemical properties of the nanoprobe were characterized by using transmission electron microscope, Fourier transform infrared spectroscopy, X-ray diffraction, dynamic light scattering (DLS), and vibrating sample magnetometer. The average diameter of the resulting MNP–DGL–RGD-GX1–DOX nanoparticles (NPs) was ~150-160 nm by DLS under simulate physiological medium. In the present experimental system, the loading amount of DOX on NPs accounted for 414.4 mg/g for MNP–DGL–RGD-GX1–DOX. The results of cytotoxicity, flow cytometry, and cellular uptake consistently indicated that the MNP–DGL–RGD-GX1–DOX NPs were inclined to target HepG2 cells in selected three kinds of cells. In vitro exploration of molecular mechanism revealed that cell apoptosis was associated with the overexpression of Fas protein and the significant activation of caspase-3. In vivo magnetic resonance imaging and biodistribution study showed that the MNP–DGL–RGD-GX1–DOX formulation had high affinity to the tumor tissue, leading to more aggregation of NPs in the tumor. In vivo antitumor efficacy research verified that MNP–DGL–RGD-GX1–DOX NPs possessed significant antitumor activity and the tumor inhibitory rate reached 78.5%. These results suggested that NPs could be promising in application to early diagnosis and therapy in hepatocellular carcinoma as a specific nanoprobe. Keywords: heterogeneous dimer peptide (HDP), molecular probe, magnetic nanoparticles (MNPs), targeting, hepatocellular carcinoma (HCC)
format	article
author	Shen JM Li XX Fan LL Zhou X Han JM Jia MK Wu LF Zhang XX Chen J
author_facet	Shen JM Li XX Fan LL Zhou X Han JM Jia MK Wu LF Zhang XX Chen J
author_sort	Shen JM
title	Heterogeneous dimer peptide-conjugated polylysine dendrimer-Fe3O4 composite as a novel nanoscale molecular probe for early diagnosis and therapy in hepatocellular carcinoma
title_short	Heterogeneous dimer peptide-conjugated polylysine dendrimer-Fe3O4 composite as a novel nanoscale molecular probe for early diagnosis and therapy in hepatocellular carcinoma
title_full	Heterogeneous dimer peptide-conjugated polylysine dendrimer-Fe3O4 composite as a novel nanoscale molecular probe for early diagnosis and therapy in hepatocellular carcinoma
title_fullStr	Heterogeneous dimer peptide-conjugated polylysine dendrimer-Fe3O4 composite as a novel nanoscale molecular probe for early diagnosis and therapy in hepatocellular carcinoma
title_full_unstemmed	Heterogeneous dimer peptide-conjugated polylysine dendrimer-Fe3O4 composite as a novel nanoscale molecular probe for early diagnosis and therapy in hepatocellular carcinoma
title_sort	heterogeneous dimer peptide-conjugated polylysine dendrimer-fe3o4 composite as a novel nanoscale molecular probe for early diagnosis and therapy in hepatocellular carcinoma
publisher	Dove Medical Press
publishDate	2017
url	https://doaj.org/article/96d16e45c06a4ce786b184009df4120d
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Heterogeneous dimer peptide-conjugated polylysine dendrimer-Fe3O4 composite as a novel nanoscale molecular probe for early diagnosis and therapy in hepatocellular carcinoma

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