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Degradable Cationic Nanohydrogel Particles for Stimuli‐Responsive Release of siRNA
Author(s) -
Nuhn Lutz,
Braun Lydia,
Overhoff Iris,
Kelsch Annette,
Schaeffel David,
Koynov Kaloian,
Zentel Rudolf
Publication year - 2014
Publication title -
macromolecular rapid communications
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.348
H-Index - 154
eISSN - 1521-3927
pISSN - 1022-1336
DOI - 10.1002/marc.201400458
Subject(s) - nanogel , cationic polymerization , oligonucleotide , materials science , biophysics , agarose gel electrophoresis , controlled release , nanoparticle , agarose , polymer , chemistry , nanotoxicology , nanotechnology , drug delivery , polymer chemistry , biochemistry , organic chemistry , dna , biology
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.