Improving thermal stability and efficacy of BCNU in treating glioma cells using PAA-functionalized graphene oxide

Yu-Jen Lu1,2,#, Hung-Wei Yang1,#, Sheng-Che Hung3, Chiung-Yin Huang2, Shin-Ming Li4, Chen-Chi M Ma4, Pin-Yuan Chen2, Hong-Chieh Tsai2, Kuo-Chen Wei2, Jyh-Ping Chen1 1Department of Chemical and Materials Engineering, Chang Gung University, Kwei-San, Taoyuan, Taiwan; 2Department of Neurosurgery, Chang...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Lu YJ, Yang HW, Hung SC, Huang CY, Li SM, Ma CCM, Chen PY, Tsai HC, Wei KC, Chen JP
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2012
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/cb8f1449461341768de94e3baca52517
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:cb8f1449461341768de94e3baca52517
record_format	dspace
spelling	oai:doaj.org-article:cb8f1449461341768de94e3baca525172021-12-02T01:32:46ZImproving thermal stability and efficacy of BCNU in treating glioma cells using PAA-functionalized graphene oxide1176-91141178-2013https://doaj.org/article/cb8f1449461341768de94e3baca525172012-03-01T00:00:00Zhttp://www.dovepress.com/improving-thermal-stability-and-efficacy-of-bcnu-in-treating-glioma-ce-a9610https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Yu-Jen Lu1,2,#, Hung-Wei Yang1,#, Sheng-Che Hung3, Chiung-Yin Huang2, Shin-Ming Li4, Chen-Chi M Ma4, Pin-Yuan Chen2, Hong-Chieh Tsai2, Kuo-Chen Wei2, Jyh-Ping Chen1 1Department of Chemical and Materials Engineering, Chang Gung University, Kwei-San, Taoyuan, Taiwan; 2Department of Neurosurgery, Chang Gung Memorial Hospital, Kwei-San, Taoyuan, Taiwan; 3Department of Radiology, Taipei Veterans General Hospital, Taipei, Taiwan; 4Department of Chemical Engineering, National Tsing Hua University, Hsinchu, Taiwan#These authors contributed equally to this workBackground: 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), a commercial chemotherapeutic drug for treating malignant brain tumors, has poor thermal stability and a short half-life. Immobilization of BCNU on a nanocarrier might increase the thermal stability of BCNU and extend its half-life.Methods: Nanosized graphene oxide (GO) could be modified by polyacrylic acid (PAA) to improve the aqueous solubility and increase the cell penetration efficacy of the nanocarrier. PAA&ndash;GO intended as a drug carrier for BCNU was prepared and characterized in this study. The size and thickness of PAA&ndash;GO was investigated by transmission electron microscopy and atomic force microscopy, and the presence of PAA functional groups was confirmed by electron spectroscopy for chemical analysis and thermogravimetric analysis. BCNU was conjugated to PAA&ndash;GO by covalent binding for specific killing of cancer cells, which could also enhance the thermal stability of the drug.Results: Single layer PAA&ndash;GO (about 1.9 nm) with a lateral width as small as 36 nm was successfully prepared. The optimum drug immobilization condition was by reacting 0.5 mg PAA&ndash;GO with 0.4 mg BCNU, and the drug-loading capacity and residual drug activity were 198 &micro;g BCNU/mg PAA&ndash;GO and 70%, respectively. This nanocarrier significantly prolonged the half-life of bound BCNU from 19 to 43 hours compared with free drug and showed efficient intracellular uptake by GL261 cancer cells. The in vitro anticancer efficacy of PAA&ndash;GO&ndash;BCNU was demonstrated by a 30% increase in DNA interstrand cross-linking and a 77% decrease in the IC50 value toward GL261 compared with the same dosage of free drug.Conclusion: Nanosized PAA&ndash;GO serves as an efficient BCNU nanocarrier by covalent binding. This nanocarrier will be a promising new vehicle for an advanced drug delivery system in cancer therapy.Keywords: graphene oxide, BCNU, glioma cells, drug delivery, thermal stabilityLu YJYang HWHung SCHuang CYLi SMMa CCMChen PYTsai HCWei KCChen JPDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2012, Iss default, Pp 1737-1747 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Lu YJ Yang HW Hung SC Huang CY Li SM Ma CCM Chen PY Tsai HC Wei KC Chen JP Improving thermal stability and efficacy of BCNU in treating glioma cells using PAA-functionalized graphene oxide
description	Yu-Jen Lu1,2,#, Hung-Wei Yang1,#, Sheng-Che Hung3, Chiung-Yin Huang2, Shin-Ming Li4, Chen-Chi M Ma4, Pin-Yuan Chen2, Hong-Chieh Tsai2, Kuo-Chen Wei2, Jyh-Ping Chen1 1Department of Chemical and Materials Engineering, Chang Gung University, Kwei-San, Taoyuan, Taiwan; 2Department of Neurosurgery, Chang Gung Memorial Hospital, Kwei-San, Taoyuan, Taiwan; 3Department of Radiology, Taipei Veterans General Hospital, Taipei, Taiwan; 4Department of Chemical Engineering, National Tsing Hua University, Hsinchu, Taiwan#These authors contributed equally to this workBackground: 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), a commercial chemotherapeutic drug for treating malignant brain tumors, has poor thermal stability and a short half-life. Immobilization of BCNU on a nanocarrier might increase the thermal stability of BCNU and extend its half-life.Methods: Nanosized graphene oxide (GO) could be modified by polyacrylic acid (PAA) to improve the aqueous solubility and increase the cell penetration efficacy of the nanocarrier. PAA&ndash;GO intended as a drug carrier for BCNU was prepared and characterized in this study. The size and thickness of PAA&ndash;GO was investigated by transmission electron microscopy and atomic force microscopy, and the presence of PAA functional groups was confirmed by electron spectroscopy for chemical analysis and thermogravimetric analysis. BCNU was conjugated to PAA&ndash;GO by covalent binding for specific killing of cancer cells, which could also enhance the thermal stability of the drug.Results: Single layer PAA&ndash;GO (about 1.9 nm) with a lateral width as small as 36 nm was successfully prepared. The optimum drug immobilization condition was by reacting 0.5 mg PAA&ndash;GO with 0.4 mg BCNU, and the drug-loading capacity and residual drug activity were 198 &micro;g BCNU/mg PAA&ndash;GO and 70%, respectively. This nanocarrier significantly prolonged the half-life of bound BCNU from 19 to 43 hours compared with free drug and showed efficient intracellular uptake by GL261 cancer cells. The in vitro anticancer efficacy of PAA&ndash;GO&ndash;BCNU was demonstrated by a 30% increase in DNA interstrand cross-linking and a 77% decrease in the IC50 value toward GL261 compared with the same dosage of free drug.Conclusion: Nanosized PAA&ndash;GO serves as an efficient BCNU nanocarrier by covalent binding. This nanocarrier will be a promising new vehicle for an advanced drug delivery system in cancer therapy.Keywords: graphene oxide, BCNU, glioma cells, drug delivery, thermal stability
format	article
author	Lu YJ Yang HW Hung SC Huang CY Li SM Ma CCM Chen PY Tsai HC Wei KC Chen JP
author_facet	Lu YJ Yang HW Hung SC Huang CY Li SM Ma CCM Chen PY Tsai HC Wei KC Chen JP
author_sort	Lu YJ
title	Improving thermal stability and efficacy of BCNU in treating glioma cells using PAA-functionalized graphene oxide
title_short	Improving thermal stability and efficacy of BCNU in treating glioma cells using PAA-functionalized graphene oxide
title_full	Improving thermal stability and efficacy of BCNU in treating glioma cells using PAA-functionalized graphene oxide
title_fullStr	Improving thermal stability and efficacy of BCNU in treating glioma cells using PAA-functionalized graphene oxide
title_full_unstemmed	Improving thermal stability and efficacy of BCNU in treating glioma cells using PAA-functionalized graphene oxide
title_sort	improving thermal stability and efficacy of bcnu in treating glioma cells using paa-functionalized graphene oxide
publisher	Dove Medical Press
publishDate	2012
url	https://doaj.org/article/cb8f1449461341768de94e3baca52517
work_keys_str_mv	AT luyj improvingthermalstabilityandefficacyofbcnuintreatinggliomacellsusingpaafunctionalizedgrapheneoxide AT yanghw improvingthermalstabilityandefficacyofbcnuintreatinggliomacellsusingpaafunctionalizedgrapheneoxide AT hungsc improvingthermalstabilityandefficacyofbcnuintreatinggliomacellsusingpaafunctionalizedgrapheneoxide AT huangcy improvingthermalstabilityandefficacyofbcnuintreatinggliomacellsusingpaafunctionalizedgrapheneoxide AT lism improvingthermalstabilityandefficacyofbcnuintreatinggliomacellsusingpaafunctionalizedgrapheneoxide AT maccm improvingthermalstabilityandefficacyofbcnuintreatinggliomacellsusingpaafunctionalizedgrapheneoxide AT chenpy improvingthermalstabilityandefficacyofbcnuintreatinggliomacellsusingpaafunctionalizedgrapheneoxide AT tsaihc improvingthermalstabilityandefficacyofbcnuintreatinggliomacellsusingpaafunctionalizedgrapheneoxide AT weikc improvingthermalstabilityandefficacyofbcnuintreatinggliomacellsusingpaafunctionalizedgrapheneoxide AT chenjp improvingthermalstabilityandefficacyofbcnuintreatinggliomacellsusingpaafunctionalizedgrapheneoxide
_version_	1718403040600391680

Improving thermal stability and efficacy of BCNU in treating glioma cells using PAA-functionalized graphene oxide

Ejemplares similares