Docetaxel-loaded solid lipid nanoparticles suppress breast cancer cells growth with reduced myelosuppression toxicity
Yuan, Qing3; Han, Jing3,4; Cong, Wenshu3; Ge, Ying2; Ma, Dandan2,3,5; Dai, Zhaoxia2,5; Li, Yaping1; Bi, Xiaolin2,3,5
刊名INTERNATIONAL JOURNAL OF NANOMEDICINE
2014
卷号9页码:4829-4846
关键词docetaxel docetaxel-loaded solid lipid nanoparticles breast cancer toxicity
ISSN号1178-2013
DOI10.2147/IJN.S70919
文献子类Article
英文摘要Docetaxel is an adjuvant chemotherapy drug widely used to treat multiple solid tumors; however, its toxicity and side effects limit its clinical efficacy. Herein, docetaxel-loaded solid lipid nanoparticles (DSNs) were developed to reduce systemic toxicity of docetaxel while still keeping its anticancer activity. To evaluate its anticancer activity and toxicity, and to understand the molecular mechanisms of DSNs, different cellular, molecular, and whole genome transcription analysis approaches were utilized. The DSNs showed lower cytotoxicity compared with the commercial formulation of docetaxel (Taxotere(R)) and induced more apoptosis at 24 hours after treatment in vitro. DSNs can cause the treated cancer cells to arrest in the G2/M phase in a dose-dependent manner similar to Taxotere. They can also suppress tumor growth very effectively in a mice model with human xenograft breast cancer. Systemic analysis of gene expression profiles by microarray and subsequent verification experiments suggested that both DSNs and Taxotere regulate gene expression and gene function, including DNA replication, DNA damage response, cell proliferation, apoptosis, and cell cycle regulation. Some of these genes expressed differentially at the protein level although their messenger RNA expression level was similar under Taxotere and DSN treatment. Moreover, DSNs improved the main side effect of Taxotere by greatly lowering myelosuppression toxicity to bone marrow cells from mice. Taken together, these results expound the antitumor efficacy and the potential working mechanisms of DSNs in its anticancer activity and toxicity, which provide a theoretical foundation to develop and apply a more efficient docetaxel formulation to treat cancer patients.
资助项目National Basic Research Program of China (973 Program)[2010CB934004] ; National Basic Research Program of China (973 Program)[2010CB934003] ; National Natural Science Foundation of China[00000000] ; Program of Changjiang Scholar and Innovative Research Team in University[IRT13049] ; CAS Knowledge Innovation Program[00000000]
WOS关键词IN-VIVO ; OVARIAN-CANCER ; PHARMACOKINETICS ; CYTOTOXICITY ; APOPTOSIS ; DELIVERY ; FORMULATION ; PACLITAXEL ; LIPOSOMES ; MICELLES
WOS研究方向Science & Technology - Other Topics ; Pharmacology & Pharmacy
语种英语
出版者DOVE MEDICAL PRESS LTD
WOS记录号WOS:000343168000001
内容类型期刊论文
源URL[http://119.78.100.183/handle/2S10ELR8/277262]  
专题药物制剂研究中心
通讯作者Li, Yaping
作者单位1.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China
2.Dalian Med Univ, Inst Canc Stem Cell, Ctr Canc, Dalian, Peoples R China;
3.Chinese Acad Sci, Inst High Energy Phys, CAS Key Lab Biol Effects Nanomat & Nanosafety, Shanghai 201203, Peoples R China;
4.Anhui Univ, Sch Life Sci, Hefei 230039, Peoples R China;
5.Dalian Med Univ, Grad Sch, Dalian, Peoples R China;
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GB/T 7714
Yuan, Qing,Han, Jing,Cong, Wenshu,et al. Docetaxel-loaded solid lipid nanoparticles suppress breast cancer cells growth with reduced myelosuppression toxicity[J]. INTERNATIONAL JOURNAL OF NANOMEDICINE,2014,9:4829-4846.
APA Yuan, Qing.,Han, Jing.,Cong, Wenshu.,Ge, Ying.,Ma, Dandan.,...&Bi, Xiaolin.(2014).Docetaxel-loaded solid lipid nanoparticles suppress breast cancer cells growth with reduced myelosuppression toxicity.INTERNATIONAL JOURNAL OF NANOMEDICINE,9,4829-4846.
MLA Yuan, Qing,et al."Docetaxel-loaded solid lipid nanoparticles suppress breast cancer cells growth with reduced myelosuppression toxicity".INTERNATIONAL JOURNAL OF NANOMEDICINE 9(2014):4829-4846.
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