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Exploring the relationship of hyaluronic acid molecular weight and active targeting efficiency for designing hyaluronic acid-modified nanoparticles

论文摘要

Although it is reported that the targeting ability of hyaluronic acid（HA）-based nanoparticles（NPs） is molecular weight（MW） dependent,the influence of HA MW on targeting efficiency of HA-functionalized NPs and the underlying mechanism remain elusive. In this study,we constituted three HA-functionalized Dox-loaded NPs（Dox/HCVs） different HA MWs（7,63,and 102 k Da） and attempted to illustrate the effects of HA MW on the targeting efficiency.The three Dox/HCVs had similar physiochemical and pharmaceutical characteristics,but showed different affinity to CD44 receptor. Furthermore,Dox/HCV-63 exerted the best targeting effect and the highest cytotoxicity compared with Dox/HCV-7 and Dox/HCV-102. It was interesting to found that both the HA-CD44 binding affinity and induced CD44 clustering by HA-based NPs were HA MW-dependent,the two of which determine the apparent targeting efficacy of Dox/HCV NPs in the conflicting directions. Those results laid a good foundation for rationally designing HA-based NPs in cancer therapy.

论文目录

  • 1. Introduction
  • 2. Materials and methods
  •   2.1. Materials
  •   2.2. Synthesis and characterization of HPCD grafted HA conjugates（HA-CDs）
  •   2.3. Preparation and characterization of Dox-loaded HA-CDs nanoparticles（Dox/HCVs）
  •   2.4. In vitro release profiles of Dox-loaded preparations
  •   2.5. Cell culture growth and maintenance
  •   2.6. Analysis of cell surface CD44
  •   2.7. Proliferation inhibition experiments
  •   2.8. Cellular uptake of Dox/HCVs
  •   2.9. Potential mechanism of nanoparticle endocytosis
  • 3. Results and discussion
  •   3.1. The synthesis and characterization of HA-CDs
  •   3.2. Characterization of Dox/HCVs
  •   3.3. CD44 receptor expression analysis
  •   3.4. Influence of HA MW on cytotoxicity of Dox-loaded formulations
  •   3.5. Effect of HA MW on cellular uptake of Dox/HCVs
  •   3.6. Potential mechanisms of nanoparticles endocytosis
  •   3.7. Influence of HA MW on the binding affinity of Dox/HCVs
  •   3.8. Effect of Dox/HCVs towards to CD44 receptors
  • 4. Conclusion
  • Conflicts of interest
  • Supplementary material

    • 文章来源

    类型: 期刊论文

    作者: Lu Zhong,Yanying Liu,Lu Xu,Qingsong Li,Dongyang Zhao,Zhenbao Li,Huicong Zhang,Haotian Zhangb,Qiming Kan,Jin Sun,Zhonggui He

    来源: Asian Journal of Pharmaceutical Sciences 2019年05期

    年度: 2019

    分类: 医药卫生科技,工程科技Ⅰ辑

    专业: 有机化工,药学

    单位: Wuya College of Innovation,Shenyang Pharmaceutical University,School of Pharmacy,Shenyang Pharmaceutical University

    基金: supported by the National Basic Research Program of China (No. 81573371),the key projects of Liaoning Province Department of Education (No. 2017LZD03)

    分类号: R943

    页码: 521-530

    总页数: 10

    文件大小: 7231K

    下载量: 13

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