Abstract
Small interfering RNAs (siRNA) have enabled novel, specific, and efficient treatment of diseases, including
cancer. To obtain sufficient and well-controlled intracellular delivery, a drug delivery system is essential. Herein
a delivery system for siRNA, composed of cationic biodegradable nanogels, is presented. p(DEAEMA-co-HEMA-g-
PEGMA) nanogels with varying ratios of 2-diethyl aminoethyl methacrylate (DEAEMA) and 2-Hydroxyethyl
methacrylate (HEMA), crosslinked with tetraethylene glycol dimethacrylate or disulfide-crosslinker bis(2-
methacryloyloxy ethyl), are synthesized. The pH-depended nanogel swelling facilitates siRNA loading and
endosomal disruption. The disulfide-crosslinker ensures siRNA release by GSH-mediated particle disassociating.
The nanogels are within the sub-100nm range in their collapsed state, have a PDI = 0.4, and a .-potential ranging
from approximately 5-10 in the swollen state and 22–30V in the collapsed state and have a swelling ratio up to
1.6 in diameter. Furthermore, the nanogels show good serum-stability, and are capable of delivering siRNA with
acceptable cytotoxicity levels. The nanogels induced >90% eGFP-silencing in lung cancer cells, and genesilencing
of the cancer target POLR2A led to siRNA-induced cell death in squamous carcinoma cells. The findings
suggest that the nanogel-system may function as a carrier vehicle for cytoplasmic delivery of siRNA.
cancer. To obtain sufficient and well-controlled intracellular delivery, a drug delivery system is essential. Herein
a delivery system for siRNA, composed of cationic biodegradable nanogels, is presented. p(DEAEMA-co-HEMA-g-
PEGMA) nanogels with varying ratios of 2-diethyl aminoethyl methacrylate (DEAEMA) and 2-Hydroxyethyl
methacrylate (HEMA), crosslinked with tetraethylene glycol dimethacrylate or disulfide-crosslinker bis(2-
methacryloyloxy ethyl), are synthesized. The pH-depended nanogel swelling facilitates siRNA loading and
endosomal disruption. The disulfide-crosslinker ensures siRNA release by GSH-mediated particle disassociating.
The nanogels are within the sub-100nm range in their collapsed state, have a PDI = 0.4, and a .-potential ranging
from approximately 5-10 in the swollen state and 22–30V in the collapsed state and have a swelling ratio up to
1.6 in diameter. Furthermore, the nanogels show good serum-stability, and are capable of delivering siRNA with
acceptable cytotoxicity levels. The nanogels induced >90% eGFP-silencing in lung cancer cells, and genesilencing
of the cancer target POLR2A led to siRNA-induced cell death in squamous carcinoma cells. The findings
suggest that the nanogel-system may function as a carrier vehicle for cytoplasmic delivery of siRNA.
| Original language | English |
|---|---|
| Article number | 104510 |
| Journal | Journal of Drug Delivery Science and Technology |
| Volume | 86 |
| Number of pages | 13 |
| ISSN | 1773-2247 |
| DOIs | |
| Publication status | Published - Sept 2023 |
Keywords
- Biodegradable nanoparticles
- Nanogels
- Stimuli-responsive nanogel system
- siRNA delivery