Langmuir film approach with breast cancer and fibroblast cell membranes to explore their interaction with doxorubicin

Abstract

Hypothesis The interaction between doxorubicin (DOX), a widely used chemotherapeutic agent, and cellular membranes significantly influences its therapeutic efficacy and selectivity. This study hypothesizes that membrane composition differences between breast cancer (MCF-7) and healthy fibroblast (FB) cells lead to distinct interactions with DOX. Experiments Langmuir films were created using isolated membranes from MCF-7 and FB cells, and surface pressure–area isotherms and compression-expansion cycles were recorded. Morphological features were evaluated through micro-Brewster angle microscopy (MicroBAM) and atomic force microscopy (AFM). DOX was introduced into the subphase to study its interaction with both membranes upon compression and over time in preformed films. Findings The high reproducibility of surface pressure-area isotherms and the minimal hysteresis in compression-expansion cycles confirm that cell membranes form stable Langmuir films. MCF-7 film isotherms exhibited larger molecular areas than FB films, indicating a more expanded state due to protein overexpression and lipid differences, but both displayed a similar surface compression modulus. Interaction with DOX differed between the MCF-7 and FB membranes, primarily due to the different electrostatic charges within the membrane components. DOX insertion increased hysteresis in both membrane types. At low pressures, DOX penetrated both films, whereas at high pressures it internalized more in FB films, likely due to hydrophobic interactions. DOX induces membrane aggregation, with more pronounced effects on MCF-7 membranes due to stronger electrostatic interactions. This study demonstrates the advantages of real cell membrane Langmuir films over lipid models in membrane-drug interaction studies.