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基于点击化学修饰的肿瘤靶向阿霉素脂质体的制备与表征

尚云凯, 鞠曹云, 谢达平, 张灿

尚云凯, 鞠曹云, 谢达平, 张灿. 基于点击化学修饰的肿瘤靶向阿霉素脂质体的制备与表征[J]. 中国药科大学学报, 2016, 47(6): 708-713. DOI: 10.11665/j.issn.1000-5048.20160613
引用本文: 尚云凯, 鞠曹云, 谢达平, 张灿. 基于点击化学修饰的肿瘤靶向阿霉素脂质体的制备与表征[J]. 中国药科大学学报, 2016, 47(6): 708-713. DOI: 10.11665/j.issn.1000-5048.20160613
SHANG Yunkai, JU Caoyun, XIE Daping, ZHANG Can. Preparation and characterization of tumor targeting doxorubicin liposomesmodified via click chemistry[J]. Journal of China Pharmaceutical University, 2016, 47(6): 708-713. DOI: 10.11665/j.issn.1000-5048.20160613
Citation: SHANG Yunkai, JU Caoyun, XIE Daping, ZHANG Can. Preparation and characterization of tumor targeting doxorubicin liposomesmodified via click chemistry[J]. Journal of China Pharmaceutical University, 2016, 47(6): 708-713. DOI: 10.11665/j.issn.1000-5048.20160613

基于点击化学修饰的肿瘤靶向阿霉素脂质体的制备与表征

基金项目: 国家自然科学基金资助项目(No.81273468,No.81473153,No.81503003)

Preparation and characterization of tumor targeting doxorubicin liposomesmodified via click chemistry

  • 摘要: 首先合成了叠氮化的胆固醇和炔基化的奥曲肽,并基于叠氮化的胆固醇制备了叠氮修饰的阿霉素脂质体Dox@N3-L;随后利用点击反应在其表面修饰了具有肿瘤靶向功能的奥曲肽,得到奥曲肽靶向阿霉素脂质体Dox@Oct-L;最后考察了点击反应的进程、点击修饰对药物包封率的影响以及脂质体的体外靶向性。结果表明,通过点击反应能成功将奥曲肽修饰到载药载体表面,点击修饰对脂质体中荷载的药物没有影响,包封率为99.8%,与点击前无显著差异。细胞毒性实验结果显示,Dox@Oct-L对肿瘤细胞HepG2的杀伤作用强于Dox@N3-L,表明Dox@Oct-L对HepG2细胞具有一定的靶向性。因此,利用点击化学在荷载药物的载体表面修饰是一种温和有效的方式,可方便地实现载药载体表面的功能化。
    Abstract: In this study, octreotide targeting doxorubicin liposome(Dox@Oct-L)was prepared by modifying cholesterol with azide group to prepare azide-modified doxorubicin liposome(Dox@N3-L), followed by click reaction on the vehicle surface with alkyne-modified octreotide. HPLC chromatographic determination showed that octreotide was successfully attached to drug loaded liposome. No significant effect of click modification on the drug loaded within liposome was detected, and the entrapment efficiency of Dox@Oct-L was 99. 8%. Dox@Oct-L showed improved in vitro anti-tumor activity against HepG2 cell when compared with Dox@N3-L, demonstrating that Dox@Oct-L possessed targeting ability against HepG2 cell. Therefore, the click chemistry in modification of drug-loading carrier surface is gentle and efficient, providing the possibility to functional modification in drug-loading carrier surface convieniently.
  • [1] Anseth KS,Klok HA.Click chemistry in biomaterials,nanomedicine,and drug delivery[J].Biomacromolecules,2016,17(1):1-3.
    [2] Lai CH,Chang TC,Chuang YJ,et al.Stepwise orthogonal click chemistry toward fabrication of paclitaxel/galactose functionalized fluorescent nanoparticles for HepG2 cell targeting and delivery[J].Bioconjugate Chem,2013,24(10):1698-1709.
    [3] Sun Q,Kang Z,Xue L,et al.A collaborative assembly strategy for tumor-targeted siRNA delivery[J].J Am Chem Soc,2015,137(18):6000-6010.
    [4] Li N,Binder WH.Click-chemistry for nanoparticle-modification[J].J Mater Chem,2011,21(42):16717-16734.
    [5] Na DH, DeLuca PP. PEGylation of octreotide: I. Separation of positional isomers and stability against acylation by poly(D,L-lactide-co-glycolide)[J].Pharm Res,2005,22(5):736-742.
    [6] Na DH,Lee KC,DeLuca PP.PEGylation of octreotide:II.Effect of N-terminal mono-PEGylation on biological activity and pharmacokinetics[J].Pharm Res,2005,22(5):743-749.
    [7] Blenke EO,Klaasse G,Merten H,et al.Liposome functionalization with copper-free “click chemistry”[J].J Control Release,2015,202:14-20.
    [8] Dai W, Jin W, Zhang J, et al. Spatiotemporally controlled co-delivery of anti-vasculature agent and cytotoxic drug by octreotide-modified stealth liposomes[J].Pharm Res,2012,29(10):2902-2911.
    [9] Zhang J,Jin W,Wang X,et al.A novel octreotide modified lipid vesicle improved the anticancer efficacy of doxorubicin in somatostatin receptor 2 positive tumor models[J].Mol Pharmaceut,2010,7(4):1159-1168.
    [10] Reynaert H,Rombouts K,Vandermonde A,et al.Expression of somatostatin receptors in normal and cirrhotic human liver and in hepatocellular carcinoma[J].Gut,2004,53(8):1180-1189.
    [11] Yuan D,Sun M,Wang Y,et al.Preparation and in vitro characterization of octreotide-targeting doxorubicin liposome[J].J China Pharm Univ(中国药科大学学报),2011,42(3):223-229.
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出版历程
  • 刊出日期:  2016-12-24

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