RESUMO
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.
Assuntos
Polietilenoglicóis/química , Polietilenoimina/análogos & derivados , RNA Interferente Pequeno/administração & dosagem , RNA Interferente Pequeno/química , Animais , Linhagem Celular Tumoral , Inativação Gênica/fisiologia , Humanos , Espectroscopia de Ressonância Magnética , Masculino , Camundongos , Microscopia Confocal , Polietilenoimina/química , Interferência de RNA , Espectroscopia de Infravermelho com Transformada de Fourier , Fator A de Crescimento do Endotélio Vascular/genéticaRESUMO
Linear-like and photoluminescent polyethylenimines (LPEIs) were synthesized through a one-pot reaction within 5 min using synchrotron radiation for intracellular imaging and siRNA delivery.