Journal
NANOSCALE
Volume 6, Issue 1, Pages 521-531Publisher
ROYAL SOC CHEMISTRY
DOI: 10.1039/c3nr04794f
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Funding
- Society in Science Foundation
- National Institutes for Health [1K25CA166178, T32GM008692]
- National Science Foundation [DMR 1032187]
- Direct For Mathematical & Physical Scien
- Division Of Materials Research [1032187] Funding Source: National Science Foundation
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Tissue engineering and advanced manufacturing of human stem cells requires a suite of tools to control gene expression spatiotemporally in culture. Inducible gene expression systems offer cell-extrinsic control, typically through addition of small molecules, but small molecule inducers typically contain few functional groups for further chemical modification. Doxycycline (DXC), a potent small molecule inducer of tetracycline (Tet) transgene systems, was conjugated to a hyperbranched dendritic polymer (Boltorn H40) and subsequently reacted with polyethylene glycol (PEG). The resulting PEG-H40-DXC nanoparticle exhibited pH-sensitive drug release behavior and successfully controlled gene expression in stem-cell-derived fibroblasts with a Tet-On system. While free DXC inhibited fibroblast proliferation and matrix metalloproteinase (MMP) activity, PEG-H40-DXC nanoparticles maintained higher fibroblast proliferation levels and MMP activity. The results demonstrate that the PEG-H40-DXC nanoparticle system provides an effective tool to controlling gene expression in human stem cell derivatives.
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