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Issue 1, 2014
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Drug-loaded nanoparticles induce gene expression in human pluripotent stem cell derivatives

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Abstract

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.

Graphical abstract: Drug-loaded nanoparticles induce gene expression in human pluripotent stem cell derivatives

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Supplementary files

Article information


Submitted
08 Sep 2013
Accepted
02 Nov 2013
First published
06 Nov 2013

Nanoscale, 2014,6, 521-531
Article type
Paper

Drug-loaded nanoparticles induce gene expression in human pluripotent stem cell derivatives

V. Gajbhiye, L. Escalante, G. Chen, A. Laperle, Q. Zheng, B. Steyer, S. Gong and K. Saha, Nanoscale, 2014, 6, 521
DOI: 10.1039/C3NR04794F

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