Bimodal Tumor-Targeting from Microenvironment Responsive Hyaluronan Layer-by-Layer (LbL) Nanoparticles
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Hammond_Bimodal tumor.pdf
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Author(s)
Morton, Stephen Winford
Choi, Jae-Hyeok
Deng, Zhou J.
Cho, Nam-Joon
Shopsowitz, Kevin
Hammond, Paula T
Dreaden, Erik
Date Issued
August 2014
Journal
ACS Nano
Publisher
American Chemical Society (ACS)
Citation
Dreaden, Erik C., Stephen W. Morton, Kevin E. Shopsowitz, Jae-Hyeok Choi, Zhou J. Deng, Nam-Joon Cho, and Paula T. Hammond. “Bimodal Tumor-Targeting from Microenvironment Responsive Hyaluronan Layer-by-Layer (LbL) Nanoparticles.” ACS Nano 8, no. 8 (August 26, 2014): 8374–8382.
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Author's final manuscript
Abstract
Active targeting of nanoscale drug carriers can improve tumor-specific delivery; however, cellular heterogeneity both within and among tumor sites is a fundamental barrier to their success. Here, we describe a tumor microenvironment-responsive layer-by-layer (LbL) polymer drug carrier that actively targets tumors based on two independent mechanisms: pH-dependent cellular uptake at hypoxic tumor pH and hyaluronan-directed targeting of cell-surface CD44 receptor, a well-characterized biomarker for breast and ovarian cancer stem cells. Hypoxic pH-induced structural reorganization of hyaluronan-LbL nanoparticles was a direct result of the nature of the LbL electrostatic complex, and led to targeted cellular delivery in vitro and in vivo, with effective tumor penetration and uptake. The nanoscale drug carriers selectively bound CD44 and diminished cancer cell migration in vitro, while co-localizing with the CD44 receptor in vivo. Multimodal targeting of LbL nanoparticles is a powerful strategy for tumor-specific cancer diagnostics and therapy that can be accomplished using a single bilayer of polyamine and hyaluronan that, when assembled, produce a dynamic and responsive cell–particle interface.
MIT Department
Massachusetts Institute of Technology. Institute for Soldier Nanotechnologies
Massachusetts Institute of Technology. Department of Chemical Engineering
Koch Institute for Integrative Cancer Research at MIT
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DOI of Published Version
https://doi.org/10.1021/nn502861t
