Abstract
Purpose
In this work a novel pH-responsive nanoscale polymer network was investigated for potential applications in nanomedicine. These consisted of a polybasic core surface stabilized with poly(ethylene glycol) grafts. The ability to control swelling properties via changes in core hydrophobicity and crosslinking feed density was assessed. The nanomatrices were also evaluated in vitro as nanocarriers for targeted intracellular delivery of macromolecules.
Materials and Methods
Photo-emulsion polymerization was used to synthesize poly[2-(diethylamino)ethyl methacrylate-co-t-butyl methacrylate-g-poly(ethylene glycol)] (PDBP) nanomatrices. These were characterized using NMR, dynamic and electrophoretic light scattering, electron microscopy. The cytocompatibility and cellular uptake of nanomatrices was measured using the NIH/3T3 and A549 cell lines.
Results
PDBP nanomatrices had a dry diameter of 40–60 nm and a hydrodynamic diameter of 70–90 nm in the collapsed state. Maximum volume swelling ratios from 6–22 were obtained depending on crosslinking feed density. Controlling the hydrophobicity of the networks allowed for control over the critical swelling pH without a significant loss in maximal volume swelling. The effect of PDBP nanomatrices on cell viability and cell membrane integrity depended on crosslinking feed density. Cell uptake and cytosolic delivery of FITC-albumin was enhanced from clathrin-targeting nanocarriers. The uptake resulted in nuclear localization of the dye in a cell type dependent fashion.
Conclusions
The results of this work indicate that PDBP nanomatrices have tunable swelling properties. The networks were cytocompatible and proved to be suitable agents for intracellular delivery.
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Abbreviations
- AEM:
-
2-aminoethyl methacrylate hydrochloride
- BFA:
-
brefeldin A
- BMA:
-
tert-butyl methacrylate
- DEAEM:
-
2-(diethylamino)ethyl methacrylate)
- DLS:
-
dynamic light scattering
- FITC:
-
fluorescein isothiocyanate
- HPLC:
-
high performance liquid chromatography
- LDH:
-
lactate dehydrogenase
- MyTAB:
-
myristyltrimethylammonium bromide
- PDBP:
-
poly[2-(diethylamino)ethyl methacrylate-co-t-butyl methacrylate-g-poly(ethylene glycol)]
- PDEAEM:
-
poly[2-(diethylamino)ethyl methacrylate]
- PDGP:
-
poly[2-(diethylamino)ethyl methacrylate-g-poly(ethylene glycol)]
- PEGMMA:
-
poly(ethylene glycol) monomethyl ether monomethacrylate
- RGDS:
-
arginine-glycine-aspartate-serine
- TEGDMA:
-
Tetraethylene glycol dimethacrylate
- Tf:
-
holo-transferrin
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Acknowledgements
The authors would like to acknowledge support from the National Institutes of Health, grant number EG-000246, a National Science Foundation Integrative Graduate Education and Research Traineeship (IGERT) Fellowship (to O.Z.F.), DGE-03-33080, and the University of Texas at Austin Undergraduate Research Fellowships to T.K. and S.R.D. The authors would also like to acknowledge the assistance of the University of Texas at Austin Institute for Cellular and Molecular Biology, the Texas Materials Institute and Professor Lisa Brannon-Peppas, Ph.D. for the use of their facilities.
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Fisher, O.Z., Kim, T., Dietz, S.R. et al. Enhanced Core Hydrophobicity, Functionalization and Cell Penetration of Polybasic Nanomatrices. Pharm Res 26, 51–60 (2009). https://doi.org/10.1007/s11095-008-9704-2
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DOI: https://doi.org/10.1007/s11095-008-9704-2