Targeted therapy for human hepatic carcinoma cells using folate-functionalized polymeric micelles loaded with superparamagnetic iron oxide and sorafenib in vitro

Lei Zhang,1 Faming Gong,2 Fang Zhang,3 Jing Ma,1 Peidong Zhang,1 Jun Shen3 1Department of Hepatobiliary and Pancreatic Surgery, 2PCFM Laboratory of Ministry of Education, School of Chemistry and Chemical Engineering, 3Department of Radiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Gu...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Zhang L, Gong F, Zhang F, Ma J, Zhang P, Shen J
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2013
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/2ab273f011df443dad57b5949a397cb6
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:2ab273f011df443dad57b5949a397cb6
record_format	dspace
spelling	oai:doaj.org-article:2ab273f011df443dad57b5949a397cb62021-12-02T04:21:20ZTargeted therapy for human hepatic carcinoma cells using folate-functionalized polymeric micelles loaded with superparamagnetic iron oxide and sorafenib in vitro1176-91141178-2013https://doaj.org/article/2ab273f011df443dad57b5949a397cb62013-04-01T00:00:00Zhttp://www.dovepress.com/targeted-therapy-for-human-hepatic-carcinoma-cells-using-folate-functi-a12795https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Lei Zhang,1 Faming Gong,2 Fang Zhang,3 Jing Ma,1 Peidong Zhang,1 Jun Shen3 1Department of Hepatobiliary and Pancreatic Surgery, 2PCFM Laboratory of Ministry of Education, School of Chemistry and Chemical Engineering, 3Department of Radiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, People's Republic of China Background: The purpose of this study was to evaluate the inhibitory effect of targeted folate-functionalized micelles containing superparamagnetic iron oxide nanoparticles (SPIONs) and sorafenib on human hepatic carcinoma (HepG2) cells in vitro, and to observe the feasibility of surveillance of this targeting therapeutic effect by magnetic resonance imaging. Methods: Sorafenib and SPIONs were loaded into polymeric micelles. The targeted nanocarrier was synthesized by functionalizing the micelles with folate. Folate-free micelles loaded with sorafenib and SPIONs were used as control (nontargeted) micelles. Uptake of the nanocarrier by cells was assessed using Prussian blue staining after 1 hour of incubation with the polymeric micelles. The inhibitory effect of the targeted micelles on HepG2 cell proliferation at various concentrations of sorafenib was assessed in vitro using the methyl thiazolyl tetrazolium (MTT) assay and apoptotic analysis using flow cytometry. Magnetic resonance imaging using a clinical 1.5 T scanner was performed to detect changes in the signal intensity of cells after incubation with the targeted micelles. Results: Prussian blue staining showed significantly more intracellular SPIONs in cells incubated with the targeted micelles than those incubated with nontargeted micelles. The MTT assay showed that the average inhibitory ratio in the targeted group was significantly higher than that in the nontargeted group (38.13% versus 22.54%, P = 0.028). The mean apoptotic rate in the targeted cells, nontargeted cells, and untreated cells was 17.01%, 11.04%, and 7.89%, respectively. The apoptotic rate in the targeted cells was significantly higher than that in the nontargeted cells (P = 0.043). The T2 signal intensity on magnetic resonance imaging of cells treated with the targeted micelles decreased significantly with increasing concentrations of sorafenib in the cell culture medium, but there was no obvious decrease in signal intensity in cells treated with the nontargeted micelles. Conclusion: Folate-functionalized polymeric micelles loaded with SPIONs and sorafenib inhibited proliferation and induced apoptosis of HepG2 cells in vitro. The inhibitory events caused by targeted micelles can be monitored using clinical magnetic resonance. Keywords: folic acid, sorafenib, magnetic resonance imaging, superparamagnetic iron oxide nanoparticlesZhang LGong FZhang FMa JZhang PShen JDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2013, Iss default, Pp 1517-1524 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Zhang L Gong F Zhang F Ma J Zhang P Shen J Targeted therapy for human hepatic carcinoma cells using folate-functionalized polymeric micelles loaded with superparamagnetic iron oxide and sorafenib in vitro
description	Lei Zhang,1 Faming Gong,2 Fang Zhang,3 Jing Ma,1 Peidong Zhang,1 Jun Shen3 1Department of Hepatobiliary and Pancreatic Surgery, 2PCFM Laboratory of Ministry of Education, School of Chemistry and Chemical Engineering, 3Department of Radiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, People's Republic of China Background: The purpose of this study was to evaluate the inhibitory effect of targeted folate-functionalized micelles containing superparamagnetic iron oxide nanoparticles (SPIONs) and sorafenib on human hepatic carcinoma (HepG2) cells in vitro, and to observe the feasibility of surveillance of this targeting therapeutic effect by magnetic resonance imaging. Methods: Sorafenib and SPIONs were loaded into polymeric micelles. The targeted nanocarrier was synthesized by functionalizing the micelles with folate. Folate-free micelles loaded with sorafenib and SPIONs were used as control (nontargeted) micelles. Uptake of the nanocarrier by cells was assessed using Prussian blue staining after 1 hour of incubation with the polymeric micelles. The inhibitory effect of the targeted micelles on HepG2 cell proliferation at various concentrations of sorafenib was assessed in vitro using the methyl thiazolyl tetrazolium (MTT) assay and apoptotic analysis using flow cytometry. Magnetic resonance imaging using a clinical 1.5 T scanner was performed to detect changes in the signal intensity of cells after incubation with the targeted micelles. Results: Prussian blue staining showed significantly more intracellular SPIONs in cells incubated with the targeted micelles than those incubated with nontargeted micelles. The MTT assay showed that the average inhibitory ratio in the targeted group was significantly higher than that in the nontargeted group (38.13% versus 22.54%, P = 0.028). The mean apoptotic rate in the targeted cells, nontargeted cells, and untreated cells was 17.01%, 11.04%, and 7.89%, respectively. The apoptotic rate in the targeted cells was significantly higher than that in the nontargeted cells (P = 0.043). The T2 signal intensity on magnetic resonance imaging of cells treated with the targeted micelles decreased significantly with increasing concentrations of sorafenib in the cell culture medium, but there was no obvious decrease in signal intensity in cells treated with the nontargeted micelles. Conclusion: Folate-functionalized polymeric micelles loaded with SPIONs and sorafenib inhibited proliferation and induced apoptosis of HepG2 cells in vitro. The inhibitory events caused by targeted micelles can be monitored using clinical magnetic resonance. Keywords: folic acid, sorafenib, magnetic resonance imaging, superparamagnetic iron oxide nanoparticles
format	article
author	Zhang L Gong F Zhang F Ma J Zhang P Shen J
author_facet	Zhang L Gong F Zhang F Ma J Zhang P Shen J
author_sort	Zhang L
title	Targeted therapy for human hepatic carcinoma cells using folate-functionalized polymeric micelles loaded with superparamagnetic iron oxide and sorafenib in vitro
title_short	Targeted therapy for human hepatic carcinoma cells using folate-functionalized polymeric micelles loaded with superparamagnetic iron oxide and sorafenib in vitro
title_full	Targeted therapy for human hepatic carcinoma cells using folate-functionalized polymeric micelles loaded with superparamagnetic iron oxide and sorafenib in vitro
title_fullStr	Targeted therapy for human hepatic carcinoma cells using folate-functionalized polymeric micelles loaded with superparamagnetic iron oxide and sorafenib in vitro
title_full_unstemmed	Targeted therapy for human hepatic carcinoma cells using folate-functionalized polymeric micelles loaded with superparamagnetic iron oxide and sorafenib in vitro
title_sort	targeted therapy for human hepatic carcinoma cells using folate-functionalized polymeric micelles loaded with superparamagnetic iron oxide and sorafenib in vitro
publisher	Dove Medical Press
publishDate	2013
url	https://doaj.org/article/2ab273f011df443dad57b5949a397cb6
work_keys_str_mv	AT zhangl targetedtherapyforhumanhepaticcarcinomacellsusingfolatefunctionalizedpolymericmicellesloadedwithsuperparamagneticironoxideandsorafenibinvitro AT gongf targetedtherapyforhumanhepaticcarcinomacellsusingfolatefunctionalizedpolymericmicellesloadedwithsuperparamagneticironoxideandsorafenibinvitro AT zhangf targetedtherapyforhumanhepaticcarcinomacellsusingfolatefunctionalizedpolymericmicellesloadedwithsuperparamagneticironoxideandsorafenibinvitro AT maj targetedtherapyforhumanhepaticcarcinomacellsusingfolatefunctionalizedpolymericmicellesloadedwithsuperparamagneticironoxideandsorafenibinvitro AT zhangp targetedtherapyforhumanhepaticcarcinomacellsusingfolatefunctionalizedpolymericmicellesloadedwithsuperparamagneticironoxideandsorafenibinvitro AT shenj targetedtherapyforhumanhepaticcarcinomacellsusingfolatefunctionalizedpolymericmicellesloadedwithsuperparamagneticironoxideandsorafenibinvitro
_version_	1718401300054409216

Targeted therapy for human hepatic carcinoma cells using folate-functionalized polymeric micelles loaded with superparamagnetic iron oxide and sorafenib in vitro

Ejemplares similares