Preclinical screening of liposome-tumor interactions using breast cancer patient biopsies

One out of three cancer diagnoses in women is breast cancer. Its heterogeneity and interindividual variability make the development of targeted therapies, including nanoparticles and biologics, highly challenging, contributing to the high failure rate of new products. The tumor extracellular matrix (ECM) plays a critical role in tumor progression and may limit therapeutic efficacy by affecting drug uptake. Characterizing the physicochemical properties of both the ECM and drug formulations is therefore essential for improving targeted therapies. In this study, we developed a novel contact angle method to characterize the surface properties of tumor sections from breast cancer patients and Doxil®-like liposomes and to quantify their interactions. Doxil was chosen as a model formulation because of its demonstrated clinical success as well as the contribution of PEGylation to its clinical success. Liposomal formulations were of varying PEG content, molecular weight, and terminal groups. Liposomes decreased the contact angle proportionally with the suspension concentration, with PEGylation being the main factor contributing to this behavior. Breast cancer ECMs exhibited higher contact angles than nearby healthy tissue, particularly in advanced-stage tumors, indicating increased hydrophobicity during tumor progression. Liposome incubation of tumor sections reversed this trend, significantly reducing contact angles, with the greatest effects observed in advanced and metastatic tissues. These findings provide a novel method for quantifying liposome-tumor interactions as well as the contribution of surface PEG. The method is sensitive to formulation characteristics known to be clinically relevant, and its application to patient-derived biopsies might serve as an early-stage screening tool, thereby helping to reduce the use of animals during preclinical studies.