Author(s): Gajbhiye V, Escalante L, Chen G, Laperle A, Zheng Q, Steyer B, Gong S, Saha K. Drug-loaded nanoparticles induce gene expression in human pluripotent stem cell derivatives. Nanoscale. 2014 Jan 7;6(1):521-31. doi: 10.1039/c3nr04794f. Epub 2013 Nov 15. PMID 24232694
Journal: Nanoscale, Volume 6, Issue 1, Jan 2014
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.