Gene delivery systems are one of key issues that limit the development of gene therapy. The novel non-viral gene delivery systems fabricated via supramolecular assem- bly have begun to show increasing promising and ap...Gene delivery systems are one of key issues that limit the development of gene therapy. The novel non-viral gene delivery systems fabricated via supramolecular assem- bly have begun to show increasing promising and applica- tions in gene therapy due to its suitable nanometric size, controllable structure and excellent biocompatibility. In this review, the fundamental and recent progress of non-viral gene supramolecular assembly is reviewed. Artificial vi- ruses——the future direction of non-viral gene delivery sys- tems are also described.展开更多
Biodegradable polyamines have long been studied as potential recombinant viral gene vectors.Spermine(SPE) is an endogenous tetra-amine with excellent biocompatibility yet poor gene condensation capacity. We have previ...Biodegradable polyamines have long been studied as potential recombinant viral gene vectors.Spermine(SPE) is an endogenous tetra-amine with excellent biocompatibility yet poor gene condensation capacity. We have previously synthesized a polyspermine based on SPE and poly(ethylene glycol)(PEG)diacrylate(SPE-alt-PEG) for enhanced transfection performance, but the synthesized SPE-alt-PEG still lacked specificity towards cancer cells. In this study, folic acid(FA) was incorporated into SPE-alt-PEG to fabricate a targeted gene delivery vector(FA-SPE-PEG) via an acylation reaction. FA-SPE-PEG exhibited mild cytotoxicity in both cancer cells and normal cells. FA-SPE-PEG possessed higher transfection efficiency than PEI 25 K and Lipofectamines2000 in two tested cancer cell lines at functional weight ratios, and its superiority over untargeted SPE-alt-PEG was prominent in cells with overexpressed folate receptors(FRs). Moreover, in vivo delivery of green fluorescent protein(GFP) with FA-SPE-PEG resulted in highest fluorescent signal intensity of all investigated groups. FA-SPE-PEG showed remarkably enhanced specificity towards cancer cells both in vivo and in vitro due to the interaction between FA and FRs. Taken together, FA-SPE-PEG was demonstrated to be a prospective targeted gene delivery vector with high transfection capacity and excellent biocompatibility.展开更多
Summary: To evaluate the feasibility of using polyethyleneimine (PEI) coated magnetic iron oxide nanoparticles (polyMAG-1000) as gene vectors. The surface characteristics of the nanoparticles were observed with scanni...Summary: To evaluate the feasibility of using polyethyleneimine (PEI) coated magnetic iron oxide nanoparticles (polyMAG-1000) as gene vectors. The surface characteristics of the nanoparticles were observed with scanning electron microscopy. The ability of the nanoparticles to combine with and protect DNA was investigated at different PH values after polyMAG-1000 and DNA were combined in different ratios. The nanoparticles were tested as gene vectors with in vitro transfection models. Under the scanning electron microscope the nanoparticles were about 100 nm in diameter. The nanoparticles could bind and condense DNA under acid, neutral and alkaline conditions, and they could transfer genes into cells and express green fluorescent proteins (GFP). The transfection efficiency was highest (51 %) when the ratio of nanoparticles to DNA was 1:1 (v:w). In that ratio, the difference in transfection efficiency was marked depending on whether a magnetic field was present or not: about 10 % when it was absent but 51 % when it was present. The magnetic iron oxide nanoparticles coated with PEI may potentially be used as gene vectors.展开更多
基金This work was fnancially supported by the Natu—ral Science Foundation of Zhejiang Province(Grant No.M503151)the National Natural Science Foundation of China(Grant No 50403021).
文摘Gene delivery systems are one of key issues that limit the development of gene therapy. The novel non-viral gene delivery systems fabricated via supramolecular assem- bly have begun to show increasing promising and applica- tions in gene therapy due to its suitable nanometric size, controllable structure and excellent biocompatibility. In this review, the fundamental and recent progress of non-viral gene supramolecular assembly is reviewed. Artificial vi- ruses——the future direction of non-viral gene delivery sys- tems are also described.
基金the National Natural Science Foundation of China(Grant Nos.81573369,21301191,81570696 and 31270985)the Natural Science Foundation of Jiangsu Province,China(Grant Nos.BK20130661 and BK20140659)the Research and Innovation Project of Jiangsu Province(Grant No.KYLX15_0640)
文摘Biodegradable polyamines have long been studied as potential recombinant viral gene vectors.Spermine(SPE) is an endogenous tetra-amine with excellent biocompatibility yet poor gene condensation capacity. We have previously synthesized a polyspermine based on SPE and poly(ethylene glycol)(PEG)diacrylate(SPE-alt-PEG) for enhanced transfection performance, but the synthesized SPE-alt-PEG still lacked specificity towards cancer cells. In this study, folic acid(FA) was incorporated into SPE-alt-PEG to fabricate a targeted gene delivery vector(FA-SPE-PEG) via an acylation reaction. FA-SPE-PEG exhibited mild cytotoxicity in both cancer cells and normal cells. FA-SPE-PEG possessed higher transfection efficiency than PEI 25 K and Lipofectamines2000 in two tested cancer cell lines at functional weight ratios, and its superiority over untargeted SPE-alt-PEG was prominent in cells with overexpressed folate receptors(FRs). Moreover, in vivo delivery of green fluorescent protein(GFP) with FA-SPE-PEG resulted in highest fluorescent signal intensity of all investigated groups. FA-SPE-PEG showed remarkably enhanced specificity towards cancer cells both in vivo and in vitro due to the interaction between FA and FRs. Taken together, FA-SPE-PEG was demonstrated to be a prospective targeted gene delivery vector with high transfection capacity and excellent biocompatibility.
文摘Summary: To evaluate the feasibility of using polyethyleneimine (PEI) coated magnetic iron oxide nanoparticles (polyMAG-1000) as gene vectors. The surface characteristics of the nanoparticles were observed with scanning electron microscopy. The ability of the nanoparticles to combine with and protect DNA was investigated at different PH values after polyMAG-1000 and DNA were combined in different ratios. The nanoparticles were tested as gene vectors with in vitro transfection models. Under the scanning electron microscope the nanoparticles were about 100 nm in diameter. The nanoparticles could bind and condense DNA under acid, neutral and alkaline conditions, and they could transfer genes into cells and express green fluorescent proteins (GFP). The transfection efficiency was highest (51 %) when the ratio of nanoparticles to DNA was 1:1 (v:w). In that ratio, the difference in transfection efficiency was marked depending on whether a magnetic field was present or not: about 10 % when it was absent but 51 % when it was present. The magnetic iron oxide nanoparticles coated with PEI may potentially be used as gene vectors.