机构：[1]School of Medicine, Faculty of Health, Deakin University, Waurn Ponds, Victoria, Australia,[2]Department of Biochemistry and Molecular Biology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, P. R. China[3]School of Medical Science and Griffith Health Institute, Griffith University, Gold Coast Campus, Southport, Australia[4]Department of Surgery, Southern Clinical School, Monash University, Clayton, Victoria, Australia[5]Institute for Frontier Materials, Deakin University, Waurn Ponds, Victoria, Australia[6]Liaoning Key Laboratory of Cancer Stem Cell Research, Dalian Medical University, Dalian, China[7]Storr Liver Unit, Westmead Millennium Institute, the University of Sydney at the Westmead Hospital, Westmead, NSW, Australia
As a glycosphingolipid that can bind to several extracellular matrix proteins, sulfatide has the potential to become an effective targeting agent for tumors overexpressing tenasin-C in their microenvironment. To overcome the dose-limiting toxicity of doxorubicin (DOX), a sulfatide-containing nanoliposome (SCN) encapsulation approach was employed to improve treatment efficacy and reduce side effects of free DOX. This study analysed in vitro characteristics of sulfatide-containing nanoliposomal DOX (SCN-DOX) and assessed its cytotoxicity in vitro, as well as biodistribution, therapeutic efficacy, and systemic toxicity in a human glioblastoma U-118MG xenograft model. SCN-DOX was shown to achieve highest drug to lipid ratio (0.5∶1) and a remarkable in vitro stability. Moreover, DOX encapsulated in SCN was shown to be delivered into the nuclei and displayed prolonged retention over free DOX in U-118MG cells. This simple two-lipid SCN-DOX nanodrug has favourable pharmacokinetic attributes in terms of prolonged circulation time, reduced volume of distribution and enhanced bioavailability in healthy rats. As a result of the improved biodistribution, an enhanced treatment efficacy of SCN-DOX was found in glioma-bearing mice compared to the free drug. Finally, a reduction in the accumulation of DOX in the drug's principal toxicity organs achieved by SCN-DOX led to the diminished systemic toxicity as evident from the plasma biochemical analyses. Thus, SCN has the potential to be an effective and safer nano-carrier for targeted delivery of therapeutic agents to tumors with elevated expression of tenascin-C in their microenvironment.
基金：
National Health and Medical Research Council, Australia (#479505), and Australia-India
Strategic Research Fund Programme–Indo-Australia Science and Technology Fund (#ST040007)
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2014]版：
大类|3 区生物
小类|3 区综合性期刊
最新[2023]版：
大类|3 区综合性期刊
小类|3 区综合性期刊
第一作者：
第一作者机构：[1]School of Medicine, Faculty of Health, Deakin University, Waurn Ponds, Victoria, Australia,[2]Department of Biochemistry and Molecular Biology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, P. R. China
通讯作者：
推荐引用方式(GB/T 7714)：
Jia Lin,Sarah Shigdar,Ding Zhi Fang,et al.Improved efficacy and reduced toxicity of doxorubicin encapsulated in sulfatide-containing nanoliposome in a glioma model.[J].PloS one.2014,9(7):e103736.doi:10.1371/journal.pone.0103736.
APA：
Jia Lin,Sarah Shigdar,Ding Zhi Fang,Dognxi Xiang,Ming Q. Wei...&Wei Duan.(2014).Improved efficacy and reduced toxicity of doxorubicin encapsulated in sulfatide-containing nanoliposome in a glioma model..PloS one,9,(7)
MLA：
Jia Lin,et al."Improved efficacy and reduced toxicity of doxorubicin encapsulated in sulfatide-containing nanoliposome in a glioma model.".PloS one 9..7(2014):e103736
