Cationic trehalose-releasing nanogels complexed with oligonucleotides as putative dual-action nanocarriers

This study describes a strategy for designing dual-action nanocarriers capable of the co-release of trehalose and electrostatically bound oligonucleotides. Trehalose can reduce toxic protein aggregation and, therefore, may enhance therapeutic results in neurodegenerative diseases. Oligonucleotide therapeutics are gaining recognition for treating neurodegenerative disorders. We synthesized, characterized, and examined trehalose-releasing cationic nanogels as oligonucleotide carriers. The nanogels were prepared by photoinitiated free radical polymerization (FRP) using trehalose monoacrylate (TreA), acrylamide (AM), (3-acrylamidopropyl)trimethylammonium chloride (AMPTMAC) and trehalose diacrylate (TreDA) or N,N'-methylenebis(acrylamide) (MBAM) as crosslinkers, yielding degradable or nondegradable networks, respectively. The electrostatic complexes between nanogels and model oligonucleotide were studied by gel electrophoresis and Förster resonance energy transfer (FRET). Release studies showed that nanogels containing a higher proportion of cationic units exhibited more sustained oligonucleotide release. In addition, studies on colloidal stability, cytotoxicity, hemocompatibility and cellular uptake of nanogels and nanogel/oligonucleotide complexes were performed.