Doxorubicin and Lapatinib Combination Nanomedicine for Treating Resistant Breast Cancer

doi:10.1021/mp400687w

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

	Doxorubicin and Lapatinib Combination Nanomedicine for Treating Resistant Breast Cancer
	Wang, Huiyuan1 ; Li, Feng 2; Du, Chengan 2; Wang, Huixin 1; Mahato, Ram I.3; Huang, Yongzhuo1
刊名	MOLECULAR PHARMACEUTICS
	2014-08
卷号	11 期号:8 页码:2600-2611
关键词	polymeric micelles breast cancer multidrug resistance combination therapy lapatinib doxorubicin nanomedicine
ISSN号	1543-8384
DOI	10.1021/mp400687w
文献子类	Article
英文摘要	Our objective was to design a polymeric micelle-based doxorubicin and lapatinib combination therapy for treating multidrug resistant (MDR) breast cancers. Poly(ethylene glycol)-block-poly(2-methyl-2-benzoxycarbonylpropylene carbonate) (PEG-PBC) polymers were synthesized for preparing doxorubicin and lapatinib loaded micelles using a film dispersion method. Micelles were characterized by determining critical micelle concentration (CMC), particle size distribution, and drug loading. The anticancer effects were determined in vitro with MTT assays as well as with lactate dehydrogenase (LDH) release studies. In addition, the cellular uptake of drug-loaded micelles was determined with fluorescence microscopy and flow cytometry. Finally, in vivo anticancer activity and tolerance of developed formulations were evaluated in resistant breast tumor bearing mice. PEG(5K)-PBC7K polymer synthesized in this study had a low CMC value (1.5 mg/L) indicating an excellent dynamic stability. PEG-PBC micelles could efficiently load both doxorubicin and lapatinib drugs with a loading density of 2196 and 8.4%, respectively. The mean particle size of these micelles was 100 nm and was not affected by drug loading. The use of lapatinib as an adjuvant sensitized drug resistant MCF-7/ADR cells to doxorubicin treatment. Cellular uptake studies showed enhanced doxorubicin accumulation in MCF-7/ADR cells in the presence of lapatinib. The doxorubicin and lapatinib combination therapy showed a significant decrease in tumor growth compared to doxorubicin monotherapy. In conclusion, we have developed PEG-PBC micelle formulations for the delivery of doxorubicin and lapatinib. The combination therapy of doxorubicin plus lapatinib has a great potential for treating MDR breast cancer.
资助项目	National Basic Research Program of China (973 Program)[2013CB932503] ; National Basic Research Program of China (973 Program)[2014CB931900] ; NSFC, China[81172996] ; NSFC, China[81373357] ; Hampton University Faculty Research Award[00000000] ; Chinese Postdoctoral Science Foundation[2012M510097] ; Chinese Postdoctoral Science Foundation[2013T60478] ; Shanghai Pu-jiang Scholar Program[11PJ1411800]
WOS关键词	REVERSES MULTIDRUG-RESISTANCE ; HYBRID NANOPARTICLE SYSTEM ; BLOCK-COPOLYMER MICELLES ; DRUG-DELIVERY ; P-GLYCOPROTEIN ; CELLS ; EFFLUX ; TRANSPORTERS ; ATP ; CHEMOTHERAPY
WOS研究方向	Research & Experimental Medicine ; Pharmacology & Pharmacy
语种	英语
出版者	AMER CHEMICAL SOC
WOS记录号	WOS:000339982900010
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/276968]
专题	药物制剂研究中心
通讯作者	Li, Feng
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China; 2.Hampton Univ, Sch Pharm, Dept Pharmaceut Sci, Hampton, VA 23668 USA; 3.Univ Nebraska Med Ctr, Dept Pharmaceut Sci, Omaha, NE 68198 USA
推荐引用方式 GB/T 7714	Wang, Huiyuan,Li, Feng,Du, Chengan,et al. Doxorubicin and Lapatinib Combination Nanomedicine for Treating Resistant Breast Cancer[J]. MOLECULAR PHARMACEUTICS,2014,11(8):2600-2611.
APA	Wang, Huiyuan,Li, Feng,Du, Chengan,Wang, Huixin,Mahato, Ram I.,&Huang, Yongzhuo.(2014).Doxorubicin and Lapatinib Combination Nanomedicine for Treating Resistant Breast Cancer.MOLECULAR PHARMACEUTICS,11(8),2600-2611.
MLA	Wang, Huiyuan,et al."Doxorubicin and Lapatinib Combination Nanomedicine for Treating Resistant Breast Cancer".MOLECULAR PHARMACEUTICS 11.8(2014):2600-2611.