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101.
Maria N. Antipina Dr. Ingo Schulze Dr. Martin Heinze Bodo Dobner Prof. Dr. Andreas Langner Prof. Dr. Gerald Brezesinski Prof. Dr. 《Chemphyschem》2009,10(14):2471-2479
Investigation of DNA interactions with cationic lipids is of particular importance for the fabrication of biosensors and nanodevices. Furthermore, lipid/DNA complexes can be applied for direct delivery of DNA‐based biopharmaceuticals to damaged cells as non‐viral vectors. To obtain more effective and safer DNA vectors, the new cationic lipids 2‐tetradecylhexadecanoic acid‐{2‐[(2‐aminoethyl)amino]ethyl}amide (C I ) and 2‐tetradecylhexadecanoic acid‐2‐[bis(2‐aminoethyl)amino]ethylamide (C II ) were synthesized and characterized. The synthesis, physical–chemical properties and first transfection and toxicity experiments are reported. Special attention was focused on the capability of C I and C II to complex DNA at low and high subphase pH values. Langmuir monolayers at the air/water interface represent a well‐defined model system to study the lipid/DNA complexes. Interactions and ordering of DNA under Langmuir monolayers of the new cationic lipids were studied using film balance measurements, grazing incidence X‐ray diffraction (GIXD) and X‐ray reflectivity (XR). The results obtained demonstrate the ability of these cationic lipids to couple with DNA at low as well as at high pH value. Moreover, the observed DNA structuring seems not to depend on subphase pH conditions. An influence of the chemical structure of the lipid head group on the DNA binding ability was clearly observed. Both compounds show good transfection efficacy and low toxicity in the in vitro experiments indicating that lipids with such structures are promising candidates for successful gene delivery systems. 相似文献
102.
Yang Y Jia W Qi X Yang C Liu L Zhang Z Ma J Zhou S Li X 《Macromolecular bioscience》2004,4(12):1113-1117
This study investigated two new biodegradable polymers as gene controlled-released coatings for gene transfer. Poly(ethylene glycol)-co-poly(D,L-lactic acid) (PELA) and poly(ethylene glycol)-co-poly(lactic acid)-co-poly(glycolic acid) random copolymer (PELGA) were synthesized and used as microspheres matrices with encapsulated plasmid pCH110. The plasmid loading efficiency, cytotoxicity, transfection efficiency and in vitro degradation and release profiles of microsphere complexes were evaluated in details. The biodegradable polymers showed high DNA loading efficiency and low cytotoxicity as gene controlled-released coatings, and the poly(ethylene glycol) (PEG) contents of polymer matrices influenced the diameter, loading efficiency and transfection efficiency of plasmid DNA within the microspheres. The average diameters of PELA and PELGA microspheres were between 0.5 and 1.5 microm, and the plasmid loading efficiency was 62 and 73% for PELA and PELGA microspheres with 10% PEG content, respectively. In vitro testing showed a gradual release profile of DNA from polymeric matrices. The polymers/DNA microspheres had high transfection efficiency and early gene expression and maintenance of gene expression level for up to 96 h, although transfection efficiency were slightly lower than that of liposome in the initial 24 h. The biodegradable polymeric materials possess potential superiority as gene carriers. 相似文献
103.
《Macromolecular bioscience》2018,18(4)
The present contribution is focused on feasibility of using comb‐like copolymers of polyethylenimine with poly(2‐ethyl‐2‐oxazoline) (LPEI‐comb‐PEtOx) with varying grafting densities and degrees of polymerization of PEI and PEtOx to deliver DNA molecules into cells. The copolymers form small and well‐defined particles at elevated temperatures, which are used as platforms for binding and condensing DNA. The electrostatic interactions between particles and DNA result in formation of sub‐100 nm polyplex particles of narrow size distribution and different morphology and structure. The investigated gene delivery systems exhibit transfection efficiency dependent on the copolymer chain topology, shape of the polyplex particles, and internalization pathway. Flow cytometry shows enhanced transfection efficiency of the polyplexes with elongated and ellipsoidal morphology. The preliminary biocompatibility study on a panel of human cell lines shows that pure copolymers and polyplexes thereof are practically devoid of cytotoxicity. 相似文献
104.
Salah‐Eddine Stiriba Holger Frey Rainer Haag 《Angewandte Chemie (International ed. in English)》2002,41(8):1329-1334
Dendrimers are characterized by a combination of high end‐group functionality and a compact, precisely defined molecular structure. These characteristics can be used in biomedical applications, for example, for the amplification or multiplication of effects on a molecular level, or to create extremely high local concentrations of drugs, molecular labels, or probe moieties. A brief summary of the current state of the art in the field is given, and focuses on the application of dendrimers both in diagnostics as well as in therapy. In diagnostics, dendrimers that bear GdIII complexes are used as contrast agents in magnetic resonance imaging. DNA dendrimers have potential for routine use in high‐throughput functional genomic analysis, as well as for DNA biosensors. Dendrimers are also being investigated for therapeutics, for example, as carriers for controlled drug delivery, in gene transfection, as well as in boron neutron‐capture therapy. Furthermore, the antimicrobial activity of dendrimers has been studied. 相似文献
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Dextran‐formamidine esters (dextran‐N‐[(dimethylamino)methylene]‐β‐alanine ester) with different degrees of substitution (0.45–0.92) are synthesized in an one‐pot reaction. Dextran (Mw 60 000 g mol?1) is allowed to react with unprotected beta‐alanine and iminium chloride and investigated regarding the potential as gene delivery system for the transfer of plasmid DNA. With degrees of substitution ≥ 0.63 improved DNA binding with formation of enzymatically stable complexes of about 130–160 nm with negative surface charges are obtained. These physicochemical characteristics correlated with increasing transfection rates in CHO‐K1 cells determined by a luciferase reporter gene assay in dependency of the number of formamidine residues, N/P ratios and amount of DNA. The role of the number of formamidine groups is also highlighted by in vitro cyto‐ and hemotoxicity tests under the chosen conditions. These results indicate that dextran‐formamidine esters are a very promising material for the safe and efficient gene delivery. 相似文献
107.
Layered double hydroxides (LDHs) exhibit characteristic anion-exchange chemistry making them ideal carriers of negatively charged molecules like deoxyribonucleic acid (DNA). In this study, hydrotalcite (Mg−Al) and hydrotalcite-like compounds (Mg−Fe, Zn−Al, and Zn−Fe), also known as LDHs, were evaluated for their potential application as a carrier of DNA. LDHs were prepared by coprecipitation at low supersaturation and characterized by Powder X-ray diffraction (XRD), infrared (IR), Raman, and inductively coupled plasma—optical emission spectroscopy, scanning electron microscopy (SEM), and transmission electron microscopy (TEM). XRD patterns showed strong and sharp diffraction peaks for the (003) and (006) planes indicating well-ordered crystalline materials. TEM images yielded irregular circular to hexagonal-shaped particles of 50–250 nm in size. Varying degrees of DNA binding was observed for all the compounds, and nuclease digestion studies revealed that the LDHs afford some degree of protection to the bound DNA. Minimal toxicity was observed in human embryonic kidney (HEK293), cervical cancer (HeLa) and hepatocellular carcinoma (HepG2) cell lines with most showing a cell viability in excess of 80 %. All LDH complexes promoted significant levels of luciferase gene expression, with the DNA:Mg−Al LDHs proving to be the most efficient in all cell lines. 相似文献
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M. A. Maslov E. V. Sycheva N. G. Morozova G. A. Serebrennikova 《Russian Chemical Bulletin》1999,48(7):1369-1372
A number of positively charged lipids containing pyridinium,N-methylmorpholinium,N-methylimidazolinium, 4-N,N-dimethylaminopyridinium, and 4-N,N-dimethylcyclo-hexylammonium groups linked directly to the C(3) atom of 1,2-di-O-alkylglycerols with Br−, MsO−, and TsO− anions as counterions were synthesized.
Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 7, pp. 1381–1384, July, 1999. 相似文献