Related Experiment Videos
DNA-containing liposomes as a model for the study of cell membrane permeation by anthracycline derivatives
F Frezard1, A Garnier-Suillerot
1Laboratoire de Chimie Bionorganique, LPCB, UA CNRS 198, UFR de Santé, Médecine et Biologie Humaine, Bobigny, France.
Abstract:
The uptake of anthracycline derivatives into large unilamellar vesicles (LUV) in response to a driven force provided by DNA encapsulated inside the LUV has been investigated. Four anthracyclines have been used: adriamycin, 4'-O-tetrahydropyranyladriamycin (THP-ADR), daunorubicin (DNR), and carminomycin. No quenching of the drug fluorescence is observed through interaction of the drugs with the lipidic bilayer. Rapid quenching of drug fluorescence occurs when drugs intercalate between the base pairs of DNA. The kinetics of the decay of anthracycline fluorescence in the presence of DNA-containing liposomes can thus be used to follow the diffusion of the drug through the membrane. The initial rates of uptake, as a function of pH, and lipid bilayer permeability coefficients have been calculated for the neutral forms of THP-ADR and DNR. This system suggests that anthracycline may gain access to cells by passive diffusion of the neutral form of the drug under the action of a driven force provided by DNA in the nucleus.
Insights
Researchers studied anthracycline uptake into liposomes driven by DNA. Drug fluorescence quenching reveals DNA interaction, enabling tracking of membrane diffusion and suggesting a cellular entry mechanism.
Area of Science:
- Biochemistry
- Pharmacology
- Materials Science
Background:
- Anthracycline derivatives are crucial chemotherapeutic agents.
- Understanding drug delivery mechanisms into cells is vital for improving cancer treatment efficacy.
- Liposomes are widely explored as drug delivery vehicles.
Purpose of the Study:
- To investigate the uptake of anthracycline derivatives into large unilamellar vesicles (LUVs).
- To explore the role of encapsulated DNA as a driving force for drug uptake.
- To characterize the interaction of anthracyclines with DNA and lipid bilayers.
Main Methods:
- Utilized four anthracycline derivatives: adriamycin, 4'-O-tetrahydropyranyladriamycin (THP-ADR), daunorubicin (DNR), and carminomycin.
- Employed fluorescence quenching assays to monitor drug-DNA interactions.
- Measured drug uptake kinetics and calculated lipid bilayer permeability coefficients.
- Investigated the influence of pH on drug uptake rates.
Main Results:
- No fluorescence quenching was observed upon drug interaction with the lipid bilayer.
- Rapid fluorescence quenching occurred when anthracyclines intercalated with DNA.
- Liposome-encapsulated DNA facilitated anthracycline uptake, with kinetics measurable via fluorescence decay.
- Calculated initial uptake rates and permeability coefficients for neutral THP-ADR and DNR.
Conclusions:
- Anthracycline fluorescence quenching by DNA serves as a marker for drug intercalation.
- The kinetics of fluorescence decay can quantify drug diffusion across membranes.
- The DNA-driven uptake system in LUVs mimics a potential cellular entry mechanism.
- Anthracyclines may enter cells via passive diffusion of their neutral form, driven by nuclear DNA.