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首页> 外文期刊>Biomaterials >Nano-sized metabolic precursors for heterogeneous tumor-targeting strategy using bioorthogonal click chemistry in?vivo
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Nano-sized metabolic precursors for heterogeneous tumor-targeting strategy using bioorthogonal click chemistry in?vivo

机译：使用Bioornornonon咔哒化学的非均相肿瘤靶向策略的纳米尺寸代谢前体

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摘要

Abstract Herein, we developed nano-sized metabolic precursors (Nano-MPs) for new tumor-targeting strategy to overcome the intrinsic limitations of biological ligands such as the limited number of biological receptors and the heterogeneity in tumor tissues. We conjugated the azide group-containing metabolic precursors, triacetylated N -azidoacetyl- d -mannosamine to generation 4 poly(amidoamine) dendrimer backbone. The nano-sized dendrimer of Nano-MPs could generate azide groups on the surface of tumor cells homogeneously regardless of cell types via metabolic glycoengineering. Importantly, these exogenously generated ‘artificial chemical receptors’ containing azide groups could be used for bioorthogonal click chemistry, regardless of phenotypes of different tumor cells. Furthermore, in tumor-bearing mice models, Nano-MPs could be mainly localized at the target tumor tissues by the enhanced permeation and retention (EPR) effect, and they successfully generated azide groups on tumor cells in?vivo after an intravenous injection. Finally, we showed that these azide groups on tumor tissues could be used as ‘artificial chemical receptors’ that were conjugated to bioorthogonal chemical group-containing liposomes via in?vivo click chemistry in heterogeneous tumor-bearing mice. Therefore, overall results demonstrated that our nano-sized metabolic precursors could be extensively applied to new alternative tumor-targeting technique for molecular imaging and drug delivery system, regardless of the phenotype of heterogeneous tumor cells. Graphical abstract Display Omitted
机译：摘要在此，我们开发了用于新的肿瘤靶向策略的纳米代谢前体（纳米MPS），以克服生物配体如有限数量的生物受体和肿瘤组织的异质性的内在限制。我们将含叠氮化物组的代谢前体缀合，三乙酰化氮酰基乙酰-d-man甲酰胺至生成4多（酰胺胺）树枝状内骨架。纳米MP的纳米大尺寸可以在均匀地通过代谢甘油凝固的细胞类型均匀地在肿瘤细胞表面上产生叠氮基团。重要的是，无论不同肿瘤细胞的表型如何，这些外源产生的含叠氮杂基团的外源生成的“人工化学受体”可用于生物正交咔哒化学。此外，在携带肿瘤的小鼠模型中，纳米MPS可以通过增强的渗透和保留（EPR）效应来在靶肿瘤组织中局部地定位，并且它们在静脉注射后成功地在肿瘤细胞上产生叠氮酰基。最后，我们表明，肿瘤组织上的这些叠氮基团可以用作通过在非均相瘤小鼠中的α体内粘合到含生物正交化学基团的脂质体的“人工化学受体”。因此，总体结果表明，无论多均相肿瘤细胞的表型如何，我们的纳米代谢前体可以广泛地应用于用于分子成像和药物递送系统的新的替代肿瘤靶向技术。省略了图形抽象显示

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  • 来源
    《Biomaterials》 |2017年第2017期|共15页
  • 作者

    Sangmin Lee; Seulhee Jung; Heebeom Koo; Jin Hee Na; Hong Yeol Yoon; Man Kyu Shim; Jooho Park; Jong-Ho Kim; Seulki Lee; Martin G. Pomper; Ick Chan Kwon; Cheol-Hee Ahn; Kwangmeyung Kim;

  • 作者单位

    Department of Pharmacy College of Pharmacy Wonkwang University Jeonbuk;

    Center for Theragnosis Biomedical Research Institute Korea Institute of Science and Technology;

    Department of Medical Lifescience College of Medicine The Catholic Univerisity of Korea;

    Center for Theragnosis Biomedical Research Institute Korea Institute of Science and Technology;

    Center for Theragnosis Biomedical Research Institute Korea Institute of Science and Technology;

    Center for Theragnosis Biomedical Research Institute Korea Institute of Science and Technology;

    Center for Theragnosis Biomedical Research Institute Korea Institute of Science and Technology;

    Department of Pharmacy Graduate School Kyung Hee University;

    The Russell H. Morgan Department of Radiology and Radiological Science Johns Hopkins University;

    The Russell H. Morgan Department of Radiology and Radiological Science Johns Hopkins University;

    Center for Theragnosis Biomedical Research Institute Korea Institute of Science and Technology;

    Research Institute of Advanced Materials (RIAM) Department of Materials Science and Engineering;

    Center for Theragnosis Biomedical Research Institute Korea Institute of Science and Technology;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 生物医学工程;
  • 关键词

    Click chemistry; Polymerized metabolic precursors; Tumor heterogeneity; Metabolic glycoengineering; Tumor targeting;

    机译：点击化学;聚合代谢前体;肿瘤异质性;代谢甘油;肿瘤靶向;

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