A new study from the University of Barcelona has analyzed the viability of a novel nanomolecule as a drug delivery vehicle. The results, published in the journal Colloids and Surfaces B: Biointerfaces, show that liposomes designed by researchers are able to transport and deliver an anticancer drug that served as a model inside cells. The study included the participation of researchers from the Faculties of Biology, Physics and Pharmacy and Food Sciences of the University of Barcelona, as well as researchers from the Scientific and Technological Centers of the UB (CCiTUB), the Institute of nanosciences and nanotechnology of the UB (IN2UB) and the Institute of Bioengineering of Catalonia (IBEC).
Interaction between liposomes and the cell membrane
A liposome is an artificial spherical vesicle with a membrane made up of a double layer of lipids which is similar in structure to cell membranes. Since these molecules were discovered in the 1960s, they have been used as a model to study cell membranes and as a potential drug delivery system.
One of the challenges in turning liposomes into drug delivery vehicles is to discover how they interact with cell membranes and which basic mechanism – adsorption, fusion or endocytosis, or a combination of these three – is involved in the process. integration of liposomes by cells. “The interactions between liposomes and the cell membrane can be extremely different depending on the nature of the cell membrane and the lipid composition of the liposomes,” note the researchers.
The liposomes designed by the UB team are small lipid spheres whose composition is close to that of the cell they wish to treat. “This similarity facilitates its incorporation and the delivery of the drug inside the cell”, notes Òscar Domenech, member of IN2UB and one of the researchers who took part in the study.
Study in cell cultures
This study is a continuation of a previous study conducted by the same research team which analyzed the fusion mechanisms of liposomes using a simplified model copying the membrane of HeLa cells, a type of cultured cells. widely used in scientific research. “The HeLa cell membrane is more complex than the model we used in the previous study. Now, we have used real cell cultures in order to get a better view of the interaction mechanism of our liposomes,” explain the researchers.
To study the interaction between liposomes and the cell membrane and assess the integration of these nanomolecules, the researchers combined two techniques. On the one hand, they used confocal fluorescence, which allows them to see fluorescent molecules inside the cell. Next, the liposomes encapsulated calcein, a fluorescent dye, to see if the nanomolecule and its contents entered the cells.
On the other hand, the researchers used the technique of atomic force microscopy to see the physicochemical changes of the cell surface and to evaluate the rigidity of the cell membrane in the presence of liposomes. The interaction of the liposomes designed by the researchers confirmed the results obtained with model membranes and shows the formulation capacity of these nanomolecules as a potential nanocarrier. “We show that the lipid composition allows delivery of the liposome content inside the cell, as well as the effect of filopodia – small flagella of the cell – to facilitate the arrival of liposomes to the cell membrane”, adds Oscar Domenech.
A test with an anti-cancer drug
To validate the capacity of these liposomes as a drug delivery system, the researchers encapsulated methotrexate, an immunosuppressive drug used in the treatment of several oncological, inflammatory and autoimmune pathologies. “We were able to show that our liposomes are ideal for delivering this model molecule, which we know can eliminate cancer cells,” notes Domènech.
These results open the door to future studies with other molecules and cell types. “Our interest would be to extend the methodology to other types of cells or even tissues to show the viability of the analysis, as well as to use other therapeutic molecules encapsulated in liposomes”, specifies Domènech. “In addition – he adds – the two techniques that we applied during the study allowed us to obtain results in a rapid and minimally invasive way, which might in the future be indicators of the proper functioning of a drug once morest cancer cells. »
