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  • Synergetic Combinations of Dual-Targeting Ligands for Enhanced In Vitro and In Vivo Tumor Targeting

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    Accepted Manuscript (AM)
    Author(s)
    Liu, Yun
    Hui, Yue
    Ran, Rui
    Yang, Guang-Ze
    Wibowo, David
    Wang, Hao-Fei
    Middelberg, Anton PJ
    Zhao, Chun-Xia
    Griffith University Author(s)
    Wibowo, David
    Year published
    2018
    Metadata
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    Abstract
    The concept of dual‐ligand targeting has been around for quite some time, but remains controversial due to the intricate interplay between so many different factors such as the choice of dual ligands, their densities, ratios and length matching, etc. Herein, the synthesis of a combinatorial library of single and dual‐ligand nanoparticles with systematically varied properties (ligand densities, ligand ratios, and lengths) for tumor targeting is reported. Folic acid (FA) and hyaluronic acid (HA) are used as two model targeting ligands. It is found that the length matching and ligand ratio play critical roles in achieving the ...
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    The concept of dual‐ligand targeting has been around for quite some time, but remains controversial due to the intricate interplay between so many different factors such as the choice of dual ligands, their densities, ratios and length matching, etc. Herein, the synthesis of a combinatorial library of single and dual‐ligand nanoparticles with systematically varied properties (ligand densities, ligand ratios, and lengths) for tumor targeting is reported. Folic acid (FA) and hyaluronic acid (HA) are used as two model targeting ligands. It is found that the length matching and ligand ratio play critical roles in achieving the synergetic effect of the dual‐ligand targeting. When FA is presented on the nanoparticle surface through a 5K polyethylene glycol (PEG) chain, the dual ligand formulations using the HA with either 5K or 10K length do not show any targeting effect, but the right length of HA (7K) with a careful selection of the right ligand ratio do enhance the targeting efficiency and specificity significantly. Further in vitro 3D tumor spheroid models and in vivo xenograft mice models confirm the synergetic targeting efficiency of the optimal dual‐ligand formulation (5F2H7K). This work provides a valuable insight into the design of dual‐ligand targeting nanosystems.
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    Journal Title
    Advanced Healthcare Materials
    DOI
    https://doi.org/10.1002/adhm.201800106
    Copyright Statement
    © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. This is the peer reviewed version of the following article: Synergetic Combinations of Dual‐Targeting Ligands for Enhanced In Vitro and In Vivo Tumor Targeting, Advanced Healthcare Materials, Volume7, Issue15, August 8, 2018, which has been published in final form at https://doi.org/10.1002/adhm.201800106. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving (http://olabout.wiley.com/WileyCDA/Section/id-828039.html)
    Note
    This publication has been entered into Griffith Research Online as an Advanced Online Version.
    Subject
    Medicinal and biomolecular chemistry
    Biomedical engineering
    Biomaterials
    Medical biotechnology
    Nanobiotechnology
    Publication URI
    http://hdl.handle.net/10072/384892
    Collection
    • Journal articles

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