Increased poly(ethylene glycol) density decreases transfection efficacy of siRNA/poly(ethylene imine) complexes
2016
Steven Rheiner | Younsoo Bae
Small interfering RNA (siRNA) inhibits specific gene expression in cells to treat genetic diseases including cancer, but siRNA-based cancer therapy is often hindered by inefficient siRNA delivery to tumor. Poly(ethylene glycol)-conjugated poly(ethylene imine) (PEG-PEI) is widely studied as a promising siRNA carrier. PEG-PEI can form ion complexes with siRNA and enhance siRNA gene silencing (transfection) due to its high buffering capacity. However, the transfection efficacy of PEG-PEI formulations changes due to variable polymer compositions. This study investigates the effects of PEG-related factors [molecular weight (PEG MW), substitution rate (PEG%), and short PEI contaminants] on siRNA transfection efficiency of PEG-PEI in a model human colon cancer cell line (HT29). High PEG density increased PEG-PEI mass to form complexes yet decreased in vitro transfection efficiency. Low PEG MW (550 Da, 2 kDa, and 5 kDa) induced complexation between PEG-PEI and siRNA at a reduced charge ratio (N/P ratio). Dialysis removed short PEI contaminants, and the dialyzed PEI with PEG (PEG-PEI-d) formed siRNA complexes with minimal particle size distribution than PEG-PEI. siRNA/PEG-PEI-d complexes showed transfection efficiency similar to siRNA/PEG-PEI complexes at a lower N/P ratio. These results conclude that PEG MW, density, and small PEI contaminants are three major factors influencing transfection of siRNA/PEI complexes.
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