Novel lipophilic chloroquine analogues for a highly efficient gene transfer into gynecological tumors

Keil, Oliver; Bojar, Hans; Prisack, Hans-Bernd; Dall, P.

doi:10.1016/s0960-894x(01)00516-9

Cited by 15 publications

(13 citation statements)

References 7 publications

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“…CQ and memantine share the feature of being lipophilic, suggesting that they act via incorporation into the lipid bilayer [17,35,36]. When the surface membrane is exposed to these compounds, their protonated groups can be attracted to the gate within MEP-induced channel, whereas the lipophilic ones would strongly bind to the hydrophobic groups in the channel lining, thereby effectively preventing access of ions to the pore of the channel.…”

Section: Discussionmentioning

confidence: 99%

Investigations into the Correlation Properties of Membrane Electroporation-Induced Inward Currents: Prediction of Pore Formation

Yeh

et al. 2011

Cell Biochem Biophys

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Membrane electroporation (MEP) induces a drastic change in membrane conductance and permeability. However, the underlying mechanisms by which MEP-induced currents (I(MEP)) are generated or resealed remain unclear. In this study, we investigated how the fluctuations of I(MEP) might be elicited in different types of cells, including pituitary GH(3) cells, NG108-15 neuronal cells, and RAW 264.7 macrophages. We applied the detrended fluctuation analysis (DFA) to analyze the current signals in response to large hyperpolarizations. The DFA exponents from the current signals at 10 s preceding the start of the initial I(MEP) (I(Pre)) in GH(3) cells exhibited two components (short time lag [α(1)] and long time lag [α(2)]) with a crossover threshold of about 7 ms. The α(1) value was 0.46 ± 0.04 (n = 7), whereas the α(2) value with 0.62 ± 0.05 (n = 7) indicated the presence of long-term correlations of current signals. However, during maximal I(MEP), the slope of double logarithmic plot was linear and estimated to be 0.99 ± 0.02 (n = 8) with no clear crossover. Upon changes in membrane polarization, neither short- nor long-range correlation was altered. Chloroquine (CQ), a lysosomotropic agent, decreased the I(MEP) amplitude with an IC(50) value of 46 μM; however, it had no effects on the scaling exponents of I(Pre) or I(MEP). Although CQ or membrane polarization altered the amplitudes of I(MEP), no changes in correlation properties of this current were detected. The scaling exponents derived from I(Pre) exhibit long-range correlations in these different types of cells, indicating there is a correlated character of the electropore dynamics that may be allowed to predict the MEP process.

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Section: Discussionmentioning

confidence: 99%

Investigations into the Correlation Properties of Membrane Electroporation-Induced Inward Currents: Prediction of Pore Formation

Yeh

et al. 2011

Cell Biochem Biophys

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“…1,2 Some of these lipofection systems, especially Fugene6t, however, are not cGMP-conform. 3 For these reasons, we tested our cGMP-quality lipids, CCQ22 and CCQ32, 3 in breast and ovarian cancer substrates.…”

Section: Discussionmentioning

confidence: 99%

“…3 For FACS analysis we used pEGFP-C1 (Clontech, Heidelberg, Germany). The control plasmid pRc/CMV was purchased from Invitrogen, Groningen, The Netherlands.…”

Section: Plasmid Dnasmentioning

confidence: 99%

“…At 2 days after lipofection of the cells with pRc/ CMVlacZ, the dual assay was carried out as described elsewhere. 3 …”

Section: Cytotoxicity Analysismentioning

confidence: 99%

“…We designed novel liposomal vectors consisting of cationic lipids, CCQ22 or CCQ32, and a helper lipid (DOPE), which can be produced at cGMP-quality. 3 All transduction techniques including lipofection result in cytotoxic side effects. 4 Different ratios of lipids (DOPE, CCQ) were used to attempt the balance of maximal gene transfer efficiency and minimal cytotoxicity.…”

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confidence: 99%

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Novel cGMP liposomal vectors mediate efficient gene transfer

et al. 2003

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Viral vector systems are the most commonly used gene transfer tools for clinical gene therapy. However, lipofection systems are potential alternatives because of lower immunogenicity and easier cGMP production, but in vivo stability and transduction efficacy need to be improved. Therefore, we investigated gene transduction efficiency of our novel cGMP cationic lipids, CCQ22 and CCQ32, by FACS analysis. Toxicity analysis was performed to determine the cytotoxic side effects of the novel lipids. To evaluate the stability of the compounds in the context of local delivery to patients with intraperitoneally metastatic ovarian cancer, gene transfer was also tested in the presence of malignant ascites. Our novel cGMP standard lipids mediated gene transfer rates of more than 50%. However, for most cell lines cytotoxic side effects were similar to our reference lipofection system. In general, ascites had no major influence on gene transduction rates with the novel lipids. Our results suggest that CCQs may compare favorably with commercially available lipofection systems. These promising results facilitate further analysis of the compounds.

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Gentherapie in der Onkologie — Was bringt die nähere Zukunft?

Dall

Bauerschmitz

2003

54. Kongress Der Deutschen Gesellschaft Für Gynäkologie Und Geburtshilfe

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Novel lipophilic chloroquine analogues for a highly efficient gene transfer into gynecological tumors

Cited by 15 publications

References 7 publications

Investigations into the Correlation Properties of Membrane Electroporation-Induced Inward Currents: Prediction of Pore Formation

Investigations into the Correlation Properties of Membrane Electroporation-Induced Inward Currents: Prediction of Pore Formation

Novel cGMP liposomal vectors mediate efficient gene transfer

Gentherapie in der Onkologie — Was bringt die nähere Zukunft?

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