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|Title:||Synergetic combinations of dual-targeting ligands for enhanced in vitro and in vivo tumor targeting|
|Citation:||Advanced Healthcare Materials, 2018; 7(15):1800106-1-1800106-11|
|Yun Liu, Yue Hui, Rui Ran, Guang-Ze Yang, David Wibowo, Hao-Fei Wang, Anton P. J. Middelberg, and Chun-Xia Zhao|
|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 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.|
|Keywords:||dual ligands; microfluidics; polymeric nanoparticles; targeted drug delivery; tumor spheroids|
|Description:||Published online: May 23, 2018|
|Rights:||© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim|
|Appears in Collections:||Chemical Engineering publications|
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