Mesoporous silica nanoparticles loading doxorubicin reverse multidrug resistance: performance and mechanism

doi:10.1039/c1nr10580a

CORC > 上海药物研究所 > 中国科学院上海药物研究所 > 药物制剂研究中心

	Mesoporous silica nanoparticles loading doxorubicin reverse multidrug resistance: performance and mechanism
	Shen, Jianan 2; He, Qianjun 1; Gao, Yu 2; Shi, Jianlin 1; Li, Yaping2
刊名	NANOSCALE
	2011
卷号	3 期号:10 页码:4314-4322
ISSN号	2040-3364
DOI	10.1039/c1nr10580a
文献子类	Article
英文摘要	Multidrug resistance (MDR) is one of the major obstacles for successful chemotherapy in cancer. One of the effective approaches to overcome MDR is to use nanoparticle-mediated drug delivery to increase drug accumulation in drug resistant cancer cells. In this work, we first report that the performance and mechanism of an inorganic engineered delivery system based on mesoporous silica nanoparticles (MSNs) loading doxorubicin (DMNs) to overcome the MDR of MCF-7/ADR (a DOX-resistant and P-glycoprotein (P-gp) over-expression cancer cell line). The experimental results showed that DMNs could enhance the cellular uptake of doxorubicin (DOX) and increase the cell proliferation suppression effect of DOX against MCF-7/ADR cells. The IC(50) of DMNs against MCF-7/ADR cells was 8-fold lower than that of free DOX. However, an improved effect of DOX in DMNs against MCF-7 cells (a DOX-sensitive cancer cell line) was not found. The increased cellular uptake and nuclear accumulation of DOX delivered by DMNs in MCF-7/ADR cells was confirmed by confocal laser scanning microscopy, and could result from the down-regulation of P-gp and bypassing the efflux action by MSNs themselves. The cellular uptake mechanism of DMNs indicated that the macropinocytosis was one of the pathways for the uptake of DMNs by MCF-7/ADR cells. The in vivo biodistribution showed that DMNs induced a higher accumulation of DOX in drug resistant tumors than free DOX. These results suggested that MSNs could be an effective delivery system to overcome multidrug resistance.
资助项目	The National Basic Research Program of China[2010CB934000] ; The National Basic Research Program of China[2007CB935800] ; National Natural Science Foundation of China[30925041] ; National Natural Science Foundation of China[50823007] ; Science and Technology Commission of Shanghai[10430712800] ; Science Foundation for Youth Scholar of State Key Laboratory of High Performance Ceramics and Superfine Microstructures[SKL201001]
WOS关键词	DRUG-DELIVERY SYSTEMS ; IN-VIVO ; MAGNETIC NANOPARTICLES ; CONTROLLED-RELEASE ; CANCER-CELLS ; CARRIERS ; SPHERES ; CYTOTOXICITY ; LIPOSOMES ; POLYMERS
WOS研究方向	Chemistry ; Science & Technology - Other Topics ; Materials Science ; Physics
语种	英语
出版者	ROYAL SOC CHEMISTRY
WOS记录号	WOS:000295618200049
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/278666]
专题	药物制剂研究中心
通讯作者	Shi, Jianlin
作者单位	1.Chinese Acad Sci, Shanghai Inst Ceram, State Key Lab High Performance Ceram & Superfine, Shanghai 200050, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Shen, Jianan,He, Qianjun,Gao, Yu,et al. Mesoporous silica nanoparticles loading doxorubicin reverse multidrug resistance: performance and mechanism[J]. NANOSCALE,2011,3(10):4314-4322.
APA	Shen, Jianan,He, Qianjun,Gao, Yu,Shi, Jianlin,&Li, Yaping.(2011).Mesoporous silica nanoparticles loading doxorubicin reverse multidrug resistance: performance and mechanism.NANOSCALE,3(10),4314-4322.
MLA	Shen, Jianan,et al."Mesoporous silica nanoparticles loading doxorubicin reverse multidrug resistance: performance and mechanism".NANOSCALE 3.10(2011):4314-4322.