Layer-by-Layer Nanoparticles with a pH-Sheddable Layer for in Vivo Targeting of Tumor Hypoxia
Author(s)Poon, Zhiyong; Chang, Dongsook; Zhao, Xiaoyong; Hammond, Paula T.; Zhao, Xiaoyong
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Inspired by the simplicity and versatility of layer-by-layer (LbL) assembly, we applied multilayered polyelectrolyte assemblies on nanoparticles to create viable systemic delivery systems. Focusing on tumor-specific delivery, LbL nanoparticles that exhibit a pH-sensitive outer stealth layer are demonstrated to target and be retained in hypoxic tumor regions. The neutral layers shed in response to acidity to reveal a charged nanoparticle surface that is readily taken up by tumor cells. The first in vivo demonstration of this mechanism of targeting is presented, as well as an initial examination of the mechanism of uptake of the nanoparticles. We further demonstrate that this concept for tumor targeting is potentially valid for a broad range of cancers, with applicability for therapies that target hypoxic tumor tissue.
DepartmentDavid H. Koch Institute for Integrative Cancer Research at MIT; Massachusetts Institute of Technology. Department of Chemical Engineering
American Chemical Society
Poon, Zhiyong, Dongsook Chang, Xiaoyong Zhao, and Paula T Hammond. Layer-by-Layer Nanoparticles with a pH-Sheddable Layer for in Vivo Targeting of Tumor Hypoxia. ACS Nano 5, no. 6 (June 28, 2011): 4284-4292.
Author's final manuscript