New nanocarrier to deliver drugs inside cells

A liposome is an artificial, spherical-shaped vesicle with a membrane composed of a double layer of lipids that closely resembles the structure of cell membranes. Since their discovery in the 1960s, these molecules have been used as a model to study cell membranes and as a promising drug delivery system.

One of the challenges of converting liposomes into drug delivery vehicles is figuring out how they interact with cell membranes and which of the basic mechanisms—adsorption, fusion, or endocytosis, or perhaps a combination of all three—is involved in liposome internalization. by the 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,” explain researchers from the faculties of Biology, Physics, and Pharmacy and Food Sciences, as well as the Scientific and Technological Centers of the University of Barcelona (UB), the Institute of Nanoscience and Nanotechnology of the UB (IN2UB) and the Institute of Bioengineering of Catalonia (IBEC).

This team has designed liposomes that are small lipid spheres with a composition similar to that of the cell to be treated. “This similarity facilitates their incorporation and the release of drugs within the cell,” says Òscar Domènech, a member of IN2UB and one of the researchers who participated in the study.

This research is the continuation of a previous study carried out by this same research team in which they analyzed the fusion mechanisms of liposomes using a simplified model that imitated the membrane of HeLa cells, a type of culture cells widely used in the scientific investigation. “The HeLa cell membrane is much more complex than the model we used in the previous study. We have now used real cell cultures to gain a better insight into the interaction mechanism of our liposomes,” the researchers detail.

To study how liposomes interact with the cell membrane and assess the internalization of these nanomolecules, Adrià Botet-Carreras’ team combined two techniques. On the one hand, confocal fluorescence was applied, which allows visualizing fluorescent molecules inside the cell. To this end, the liposomes encapsulated calcein, a fluorescent dye, in order to see if the nanomolecule and its contents entered cells.

On the other hand, the atomic force microscopy technique was also used to observe the physicochemical changes of the cell surface and to evaluate the rigidity of the cell membrane in the presence of the liposomes. The interaction of the liposomes designed by the researchers corroborated the results obtained with model membranes and demonstrates the capacity of the formulation of these nanomolecules as a potential nanocarrier. «We show that the lipid composition allows a release of the liposome contents inside the cell, as well as the effect that the cellular filopodia have [pequeños flagelos de la célula] in facilitating the arrival of the liposomes to the cell membrane”, highlights Òscar Domènech.

From left to right: Òscar Domènech, Adrià Botet-Carreras, M. Teresa Montero and Jordi Borrell, from the research team. (Photo: UB)

To validate the ability of these liposomes as a drug delivery system, the researchers encapsulated methotrexate, an immunosuppressive drug used to treat a variety of oncological, inflammatory, and autoimmune conditions. “We have been able to demonstrate that our liposomes are ideal for transporting and releasing this model molecule, which we know allows cancer cells to be killed,” summarizes Domènech.

These results open the door to future studies with other molecules and cell types. “Our interest would be to be able to extend the methodology to other types of cells or even to tissues to show the feasibility of analysis, as well as to be able to use other therapeutic molecules encapsulated in liposomes”, explains Domènech. “Furthermore, the two techniques applied during the study make it possible to quickly and minimally invasively obtain results that in the future could be indicators of the proper functioning of a drug against tumor or cancer cells,” concludes the researcher.

The study is entitled “On the uptake of cationic liposomes by cells: From changes in elasticity to internalization”. And it has been published in the academic journal Colloids and Surfaces B: Biointerfaces. (Source: UB)