A single-monomer derived linear-like PEI-co-PEG for siRNA delivery and silencing

Polyethylenimines (PEIs) are commonly used as a vehicle to deliver and protect siRNA, but the strong interaction still remains to be modulated for efficient siRNA release and silencing. Herein, a single-monomer derived linear-like PEI-co-PEG (LPEI-co-PEG, P-2) was synthesized to substantially enhance the siRNA release, but not affect the efficiency of protection. The linear-like copolymer (P-2) was only synthesized from a single-monomer by intensive synchrotron X-ray irradiation within 5 min, randomly producing both PEI and PEG segments. The counterpart vehicle, LPEI (P-1), was also synthesized for comparison. We found that the P-1 and P-2 were able to prevent siRNA against enzymatic degradation. Most importantly, efficient siRNA release (52%) was only observed in the siRNA/P-2 complexes and not in the siRNA/P-1 complexes (<5%), suggesting that the PEG segment may modulate the interaction between siRNA and P-2 segment. Specifically, P-2 as well as P-1 can emit photoluminescence; cancer cells exhibited a detectable photoluminescence after treatment with P-1 and P-2, indicative of their excellent transfection efficiency. Subsequently, the siGFP/P-2 complexes knocked down GFP with excellent efficiency (75%) above the siGFP/P-1 complexes (19%) and siGFP/Lipofectamine complexes (20%). Importantly, the siRNA with anti-VEGF function being associated with P-2 have been demonstrated an excellent efficiency in the suppression of tumor growth. (C) 2011 Elsevier Ltd. All rights reserved.