title: A single-monomer derived linear-like PEI-co-PEG for siRNA delivery and silencing.
abstract: 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.
authors.affiliation: Center for Nanomedicine Research, National Health Research Institutes, 35 Keyan Road Zhunan, Miaoli 35053, Taiwan.
authors.forename: Lin-Ren
authors.initials: LR
authors.lastname: Tsai
authors.forename: Min-Hua
authors.initials: MH
authors.lastname: Chen
authors.forename: Chih-Te
authors.initials: CT
authors.lastname: Chien
authors.forename: Meng-Kai
authors.initials: MK
authors.lastname: Chen
authors.forename: Fong-Sian
authors.initials: FS
authors.lastname: Lin
authors.forename: Kurt Ming-Chao
authors.initials: KM
authors.lastname: Lin
authors.forename: Yeu-Kuang
authors.initials: YK
authors.lastname: Hwu
authors.forename: Chung-Shi
authors.initials: CS
authors.lastname: Yang
authors.forename: Shu-Yi
authors.initials: SY
authors.lastname: Lin
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D020868:Gene Silencing / Q000502:physiology; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D018613:Microscopy, Confocal; D011092:Polyethylene Glycols / Q000737:chemistry*; D011094:Polyethyleneimine / Q000031:analogs & derivatives* / Q000737:chemistry; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000737:chemistry*; D017550:Spectroscopy, Fourier Transform Infrared; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics
chemical_list: D034741:RNA, Small Interfering; D042461:Vascular Endothelial Growth Factor A; C544016:poly(ethylene glycol)-co-poly(ethyleneimine); D011092:Polyethylene Glycols; D011094:Polyethyleneimine