Journal
MACROMOLECULAR RAPID COMMUNICATIONS
Volume 35, Issue 24, Pages 2057-2064Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/marc.201400458
Keywords
cationic nanohydrogels; degradable nanogels; redox-responsive carriers; siRNA delivery; stimuli-responsive release
Categories
Funding
- Fonds der Chemischen Industrie (FCI)
- Max Planck Graduate Center
- Johannes Gutenberg-Universitat Mainz (MPGC)
- DFG Sonderforschungsbereich [SFB 1066]
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Well-defined nanogels have become quite attractive as safe and stable carriers for siRNA delivery. However, to avoid nanoparticle accumulation, they need to provide a stimuli-responsive degradation mechanism that can be activated at the payload's site of action. In this work, the synthetic concept for generating well-defined nanohydrogel particles is extended to incorporate disulfide cross-linkers into a cationic nanonetwork for redox-triggered release of oligonucleotide payload as well as nanoparticle degradation under reductive conditions of the cytoplasm. Therefore, a novel disulfide-modified spermine cross-linker is designed that both allows disassembly of the nanogel as well as removal of cationic charge from residual polymer fragments. The degradation process is monitored by scanning electron microscopy (SEM) and fluorescence correlation spectroscopy (FCS). Moreover, siRNA release is analyzed by agarose gel electrophoresis and a fluorescent RNA detection assay. The results exemplify the versatility of the applied nanogel manufacturing process, which allows alternative stimuli-responsive core cross-linkers to be integrated for triggered oligonucleotide release as well as effective biodegradation for reduced nanotoxicity.
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