Gene therapy targeted to vascular cells repre- sents a promising approach for prevention and treatment of pathological conditions such as intimal hyperplasia, in-stent and post-angioplasty restenosis. In this context,...Gene therapy targeted to vascular cells repre- sents a promising approach for prevention and treatment of pathological conditions such as intimal hyperplasia, in-stent and post-angioplasty restenosis. In this context, polymeric non-viral gene delivery systems are a safe alternative to viral vectors but a further improvement in efficiency and cytocom- patibility is needed to improve their clinical success. Herein, a library of 24 branched polyethylenimine (bPEI) derivatives modified with hydrophobic moieties was synthesised, char- acterised and tested in vitro on primary vascular cells, aim- ing to identify delivery agents with superior transfection effi- ciency and low cytotoxicity. Low molecular weight PEIs (0.6, 1.2 and 2 kDa) were grafted with long (C18) and short (C3) aliphatic chains, featuring different unsaturation degrees and degrees of substitution. 0.6 kDa bPEI-based derivatives were generally ineffective in transfection on vascular smooth mus- cle cells (VSMCs), while among the other derivatives some promising vectors were identified. Forcing polyplexes on the cell surface by means of centrifugation invariably boosted transfection levels but increased cytotoxicity as well. Of note, a propionyl-snbstituted derivative (PEI2-PrA1, C3:0) was the most effective on both VSMCs and endothelial cells (ECs), with higher and more sustained gene expression in combi- nation with markedly lower cytotoxicity with respect to the gold standard 25 kDa bPEI. In addition, a linoleoyl-substi- tuted derivative (PEI1.2-LA6, C18:2) owing to its high effi- ciency in VSMCs and relative inefficacy in ECs, combined with tolerable cytotoxicity was proposed as a vector for spe- cific VSMCs targeting.展开更多
We assembled a ternary blend bulk heterojunction polymer solar cell(PSCs) containing P3HT(donor) and PC61BM(acceptor) incorporated with a small molecule oligomer, dihexyl-quaterthiophene(DH4T) as a third component. By...We assembled a ternary blend bulk heterojunction polymer solar cell(PSCs) containing P3HT(donor) and PC61BM(acceptor) incorporated with a small molecule oligomer, dihexyl-quaterthiophene(DH4T) as a third component. By optimizing the contents of DH4 T, we increased the power conversion efficiency of ternary P3HT:DH4T:PC61BM PSCs to 4.17% from 3.44% of binary P3HT:PC61BM PSCs under AM 1.5 G of 100 m W/cm2 intensity. The major improvement is from the increase of the short circuit current and fill factor that is due to the increased light absorption at short wavelength, the balanced charge carrier transportation and the enhanced hole evacuation by a DH4T-enriched layer at the anode interface. In this work, we demonstrated that the efficiency of the PSCs can be enhanced by using low-bandgap conjugated polymer and its oligomer as donors and fullerene derivatives as acceptors.展开更多
基金financially supported by the Natural Science and Engineering Research Council of Canada, (Discovery Grant to UludagH and Mantovani D)the Canadian Institute for Health Research (Operating grant to Uludag H)the Fonds de Recherche du Quebec sur les Natures et Technologies (Bilateral Grant to Mantovani D)
文摘Gene therapy targeted to vascular cells repre- sents a promising approach for prevention and treatment of pathological conditions such as intimal hyperplasia, in-stent and post-angioplasty restenosis. In this context, polymeric non-viral gene delivery systems are a safe alternative to viral vectors but a further improvement in efficiency and cytocom- patibility is needed to improve their clinical success. Herein, a library of 24 branched polyethylenimine (bPEI) derivatives modified with hydrophobic moieties was synthesised, char- acterised and tested in vitro on primary vascular cells, aim- ing to identify delivery agents with superior transfection effi- ciency and low cytotoxicity. Low molecular weight PEIs (0.6, 1.2 and 2 kDa) were grafted with long (C18) and short (C3) aliphatic chains, featuring different unsaturation degrees and degrees of substitution. 0.6 kDa bPEI-based derivatives were generally ineffective in transfection on vascular smooth mus- cle cells (VSMCs), while among the other derivatives some promising vectors were identified. Forcing polyplexes on the cell surface by means of centrifugation invariably boosted transfection levels but increased cytotoxicity as well. Of note, a propionyl-snbstituted derivative (PEI2-PrA1, C3:0) was the most effective on both VSMCs and endothelial cells (ECs), with higher and more sustained gene expression in combi- nation with markedly lower cytotoxicity with respect to the gold standard 25 kDa bPEI. In addition, a linoleoyl-substi- tuted derivative (PEI1.2-LA6, C18:2) owing to its high effi- ciency in VSMCs and relative inefficacy in ECs, combined with tolerable cytotoxicity was proposed as a vector for spe- cific VSMCs targeting.
基金financially supported by the National Natural Science Foundation of China(21374120)support by 100 Talents Program of the Chinese Academy of Sciences
文摘We assembled a ternary blend bulk heterojunction polymer solar cell(PSCs) containing P3HT(donor) and PC61BM(acceptor) incorporated with a small molecule oligomer, dihexyl-quaterthiophene(DH4T) as a third component. By optimizing the contents of DH4 T, we increased the power conversion efficiency of ternary P3HT:DH4T:PC61BM PSCs to 4.17% from 3.44% of binary P3HT:PC61BM PSCs under AM 1.5 G of 100 m W/cm2 intensity. The major improvement is from the increase of the short circuit current and fill factor that is due to the increased light absorption at short wavelength, the balanced charge carrier transportation and the enhanced hole evacuation by a DH4T-enriched layer at the anode interface. In this work, we demonstrated that the efficiency of the PSCs can be enhanced by using low-bandgap conjugated polymer and its oligomer as donors and fullerene derivatives as acceptors.