title: Improved efficacy and reduced toxicity of doxorubicin encapsulated in sulfatide-containing nanoliposome in a glioma model.
abstract: 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.
authors: School of Medicine, Faculty of Health, Deakin University, Waurn Ponds, Victoria, Australia; Department of Biochemistry and Molecular Biology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, P. R. China.
authors: Jia
authors: J
authors: Lin
authors: School of Medicine, Faculty of Health, Deakin University, Waurn Ponds, Victoria, Australia.
authors: Sarah
authors: S
authors: Shigdar
authors: Department of Biochemistry and Molecular Biology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, P. R. China.
authors: Ding Zhi
authors: DZ
authors: Fang
authors: School of Medicine, Faculty of Health, Deakin University, Waurn Ponds, Victoria, Australia.
authors: Dognxi
authors: D
authors: Xiang
authors: School of Medical Science and Griffith Health Institute, Griffith University, Gold Coast Campus, Southport, Australia.
authors: Ming Q
authors: MQ
authors: Wei
authors: Department of Surgery, Southern Clinical School, Monash University, Clayton, Victoria, Australia.
authors: Andrew
authors: A
authors: Danks
authors: Institute for Frontier Materials, Deakin University, Waurn Ponds, Victoria, Australia.
authors: Lingxue
authors: L
authors: Kong
authors: Liaoning Key Laboratory of Cancer Stem Cell Research, Dalian Medical University, Dalian, China.
authors: Lianghong
authors: L
authors: Li
authors: Storr Liver Unit, Westmead Millennium Institute, the University of Sydney at the Westmead Hospital, Westmead, NSW, Australia.
authors: Liang
authors: L
authors: Qiao
authors: School of Medicine, Faculty of Health, Deakin University, Waurn Ponds, Victoria, Australia.
authors: Wei
authors: W
authors: Duan
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D005260:Female; D005910:Glioma / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D007700:Kinetics; D008081:Liposomes / Q000737:chemistry*; D061986:MCF-7 Cells; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018613:Microscopy, Confocal; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D051381:Rats; D017207:Rats, Sprague-Dawley; D013433:Sulfoglycosphingolipids / Q000737:chemistry*; D014018:Tissue Distribution; D014183:Transplantation, Heterologous
chemical_list: D000903:Antibiotics, Antineoplastic; D008081:Liposomes; D013433:Sulfoglycosphingolipids; D004317:Doxorubicin