In vitro and in vivo gene-transferring characteristics of novel cationic lipids, DMKD (O,O'-dimyristyl-N-lysyl aspartate) and DMKE (O,O'-dimyristyl-N-lysyl glutamate)

2006 ◽  
Vol 115 (2) ◽  
pp. 234-241 ◽  
Author(s):  
Hong Sung Kim ◽  
In Ho Song ◽  
Jong Chul Kim ◽  
Eun Jeong Kim ◽  
Doo Ok Jang ◽  
...  
Keyword(s):  
2019 ◽  
Vol 9 (20) ◽  
pp. 4438 ◽  
Author(s):  
Amélia Silva ◽  
Carlos Martins-Gomes ◽  
Tiago Coutinho ◽  
Joana Fangueiro ◽  
Elena Sanchez-Lopez ◽  
...  

The surface properties of nanoparticles have decisive influence on their interaction with biological barriers (i.e., living cells), being the concentration and type of surfactant factors to have into account. As a result of different molecular structure, charge, and degree of lipophilicity, different surfactants may interact differently with the cell membrane exhibiting different degrees of cytotoxicity. In this work, the cytotoxicity of two cationic solid lipid nanoparticles (SLNs), differing in the cationic lipids used as surfactants CTAB (cetyltrimethylammonium bromide) or DDAB (dimethyldioctadecylammonium bromide), referred as CTAB-SLNs and DDAB-SLNs, respectively, was assessed against five different human cell lines (Caco-2, HepG2, MCF-7, SV-80, and Y-79). Results showed that the cationic lipids used in SLN production highly influenced the cytotoxic profile of the particles, with CTAB-SLNs being highly cytotoxic even at low concentrations (IC50 < 10 µg/mL, expressed as CTAB amount). DDAB-SLNs produced much lower cytotoxicity, even at longer exposure time (IC50 from 284.06 ± 17.01 µg/mL (SV-80) to 869.88 ± 62.45 µg/mL (MCF-7), at 48 h). To the best of our knowledge, this is the first report that compares the cytotoxic profile of CTAB-SLNs and DDAB-SLNs based on the concentration and time of exposure, using different cell lines. In conclusion, the choice of the right surfactant for biological applications influences the biocompatibility of the nanoparticles. Regardless the type of drug delivery system, not only the cytotoxicity of the drug-loaded nanoparticles should be assessed, but also the blank (non-loaded) nanoparticles as their surface properties play a decisive role both in vitro and in vivo.


Author(s):  
Jing Wu ◽  
Shuhe Wang ◽  
Xiang Li ◽  
Qi Zhang ◽  
Jie Yang ◽  
...  

BC15-31 is a DNA aptamer that targets heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1), which plays a crucial role in the process of pre-RNA maturation and is also essential for the rapid proliferation of tumor cells. In this research, we modified BC15-31 with a phosphorothioate (PS) backbone, LNA, and 2-O-MOE to enhance its stability and target affinity. In addition, a neutral cytidinyl lipid (DNCA) and a cationic lipid (CLD) were mixed to encapsulate modified aptamers with the aim of improving their cell permeability with low toxicity. Under the DNCA/CLD package, aptamers are mainly distributed in the nucleus. A modified sequence WW-24 showed an excellent selective anti-melanoma (A375 cells, ∼25 nM, 80%) activity, targeted to both hnRNP A1 and hnRNP A2/B1 found by the BLI experiment, and induced more early and late apoptosis in vitro, which also showed stronger antitumor effect and longer accumulation time in vivo. These results provide a new strategy for further clinical applications.


2001 ◽  
Vol 6 (4) ◽  
pp. 245-254 ◽  
Author(s):  
Anne E. Regelin ◽  
Erhard Fernholz ◽  
Harald F. Krug ◽  
Ulrich Massing

Lipofection, the transfer of genetic material into cells by means of cationic lipids, is of growing interest for in vitro and in vivo approaches. In order to identify ideal lipofection reagents in a HTS, we have developed an automated lipofection method for the transfer of reporter genes into cells and for determination of the lipofection results. The method has specifically been designed and optimized for 96-well microtiter plates and can successfully be carried out by a pipetting robot with accessory equipment. It consists of two separate parts: (1) pretransfection (preparation of liposomes, formation of lipoplexes, and lipoplex transfer to the cells) and (2) posttransfection (determination of the reporter enzyme activity and the protein content of the transfected cells). Individual steps of the lipofection method were specifically optimized—for example, lipoplex formation and incubation time as well as cell lysis, cell cultivating, and the reporter gene assay. The HTS method facilitates characterization of the transfection properties (efficiency and cytotoxicity) of large numbers of (cationic) lipids in various adherent cell types.


Pharmaceutics ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 729
Author(s):  
Natalia Sánchez-Arribas ◽  
María Martínez-Negro ◽  
Clara Aicart-Ramos ◽  
Conchita Tros de Ilarduya ◽  
Emilio Aicart ◽  
...  

Ample evidence exists on the role of interleukin-12 (IL-12) in the response against many pathogens, as well as on its remarkable antitumor properties. However, the unexpected toxicity and disappointing results in some clinical trials are prompting the design of new strategies and/or vectors for IL-12 delivery. This study was conceived to further endorse the use of gemini cationic lipids (GCLs) in combination with zwitterionic helper lipid DOPE (1,2-dioleoyl-sn-glycero-3-phosphatidyl ethanol amine) as nanovectors for the insertion of plasmid DNA encoding for IL-12 (pCMV-IL12) into cells. Optimal GCL formulations previously reported by us were selected for IL-12-based biophysical experiments. In vitro studies demonstrated efficient pCMV-IL12 transfection by GCLs with comparable or superior cytokine levels than those obtained with commercial control Lipofectamine2000*. Furthermore, the nanovectors did not present significant toxicity, showing high cell viability values. The proteins adsorbed on the nanovector surface were found to be mostly lipoproteins and serum albumin, which are both beneficial to increase the blood circulation time. These outstanding results are accompanied by an initial physicochemical characterization to confirm DNA compaction and protection by the lipid mixture. Although further studies would be necessary, the present GCLs exhibit promising characteristics as candidates for pCMV-IL12 transfection in future in vivo applications.


2017 ◽  
Vol 5 (39) ◽  
pp. 7963-7973 ◽  
Author(s):  
Y. N. Zhao ◽  
Y. Z. Piao ◽  
C. M. Zhang ◽  
Y. M. Jiang ◽  
A. Liu ◽  
...  

Replacement of quaternary ammonium headgroups by tri-ornithine in lipids improved gene delivery in vitro and in vivo with little toxicity.


2006 ◽  
Vol 26 (4) ◽  
pp. 301-324 ◽  
Author(s):  
N. Madhusudhana Rao ◽  
Vijaya Gopal

Cationic lipids are conceptually and methodologically simple tools to deliver nucleic acids into the cells. Strategies based on cationic lipids are viable alternatives to viral vectors and are becoming increasingly popular owing to their minimal toxicity. The first-generation cationic lipids were built around the quaternary nitrogen primarily for binding and condensing DNA. A large number of lipids with variations in the hydrophobic and hydrophilic region were generated with excellent transfection efficiencies in vitro. These cationic lipids had reduced efficiencies when tested for gene delivery in vivo. Efforts in the last decade delineated the cell biological basis of the cationic lipid gene delivery to a significant detail. The application of techniques such as small angle X-ray spectroscopy (SAXS) and fluorescence microscopy, helped in linking the physical properties of lipid:DNA complex (lipoplex) with its intracellular fate. This biological knowledge has been incorporated in the design of the second-generation cationic lipids. Lipid-peptide conjugates (peptoids) are effective strategies to overcome the various cellular barriers along with the lipoplex formulations methodologies. In this context, cationic lipid-mediated gene delivery is considerably benefited by the methodologies of liposome-mediated drug delivery. Lipid mediated gene delivery has an intrinsic advantage of being a biomimetic platform on which considerable variations could be built to develop efficient in vivo gene delivery protocols.


2015 ◽  
Vol 3 (1) ◽  
pp. 119-126 ◽  
Author(s):  
Yinan Zhao ◽  
Shubiao Zhang ◽  
Yuan Zhang ◽  
Shaohui Cui ◽  
Huiying Chen ◽  
...  

A novel tri-peptide cationic lipid can efficiently transfer DNA and siRNA into tumor cells and tumors of mice with little in vitro and in vivo toxicity.


1997 ◽  
Vol 94 (5) ◽  
pp. 1651-1656 ◽  
Author(s):  
N. Oudrhiri ◽  
J.-P. Vigneron ◽  
M. Peuchmaur ◽  
T. Leclerc ◽  
J.-M. Lehn ◽  
...  

2005 ◽  
Vol 435 (1) ◽  
pp. 217-226 ◽  
Author(s):  
Marc A. Ilies ◽  
Betty H. Johnson ◽  
Fred Makori ◽  
Aaron Miller ◽  
William A. Seitz ◽  
...  

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