title: Amphiphilic lipid derivatives of 3'-hydroxyurea-deoxythymidine: preparation, properties, molecular self-assembly, simulation and in vitro anticancer activity.
abstract: Lipid derivatives of nucleoside analogs and their nanoassemblies have become the research hotspot due to their unique function in cancer therapy. Six lipid derivatives of 3'-hydroxyurea-deoxythymidine were prepared with zidovudine as the raw material. The 5'-substituted lipid chains in the derivatives were from the various fatty acids including octanoic acid, decanoic acid, dodecanoic acid, tetradecanoic acid, hexadecanoic acid and octadecanoic acid corresponding to the derivatives OHT, DHT, DDHT, TDHT, HDHT and ODHT. The amphiphilic derivatives formed Langmuir monolayers at the air/water interface with different surface pressure-molecular area isotherms depending on the length of lipid chains. The nanoassemblies of OHT, DHT, DDHT, TDHT and HDHT and the nanoscale precipitates of ODHT were obtained after we injected their tetrahydrofuran solutions doped with hydrophilic long chained polymers into water. Electron microscopy showed that the morphology of nanoassemblies may be vesicles or nanotubes depending on the length of lipid chains. The shorter the lipid chains were, the softer the nanoassemblies. Computer simulation supported the experimental results. The nanoassemblies and the nanoscale precipitates showed much higher anticancer effects on SW620 cells than the parent drug hydroxyurea. The nanostructures of the derivatives are promising anticancer nanomedicines.
authors.affiliation: Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing 100850, China.
authors.forename: Miao
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing 100850, China.
authors.forename: Shuo
authors.initials: S
authors.lastname: Qi
authors.affiliation: Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing 100850, China. Electronic address: jinyg@bmi.ac.cn.
authors.forename: Yiguang
authors.initials: Y
authors.lastname: Jin
authors.affiliation: Beijing Institute of Technology, Beijing 100081, China.
authors.forename: Weishang
authors.initials: W
authors.lastname: Yao
authors.affiliation: National Center of Biomedical Analysis, Beijing 100850, China.
authors.forename: Sa
authors.initials: S
authors.lastname: Zhang
authors.affiliation: General Hospital of PLA, The First Affiliation Hospital, Beijing 100048, China. Electronic address: jameszhao304@163.com.
authors.forename: Jingyu
authors.initials: J
authors.lastname: Zhao
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D006918:Hydroxyurea / Q000737:chemistry* / Q000494:pharmacology*; D066298:In Vitro Techniques; D049329:Nanostructures; D013936:Thymidine / Q000737:chemistry*; D015215:Zidovudine / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D015215:Zidovudine; D013936:Thymidine; D006918:Hydroxyurea
keywords: Anticancer; Hydroxyurea; Langmuir monolayers; Lipid derivatives; Molecular self-assembly; Zidovudine