Abstract

Relevant 3D In vitro Models For Predictive Screening of Nanodrugs

Simona Mura, Full Professor, Université Paris-Saclay

Nanoscale systems for drug delivery have received considerable attention over the past decades, as they have the potential to overcome limits associated with conventional drug therapies, providing a solution to medical challenges that urgently require new therapeutic approaches. Nanodrugs can improve the therapeutic index of the loaded drug by providing protection against degradation, enabling controlled release and distribution, and increasing bioavailability. Advanced functionalization strategies have been used to confer them long-circulating properties  and facilitate targeting to specific cells. These efforts have led to the introduction into clinical practice of a few nanoscale systems for tumor therapy. However, their small number, compared to the variety of promising systems proposed, reveals a considerable gap between favorable preclinical results and real clinical performance. Biological barriers, inherent to tumors and their microenvironments, pose formidable challenges. To bridge this gap, our focus turns to three-dimensional (3D) culture methodologies. Unlike conventional 2D cultures, 3D models better replicate the heterogeneity, pathophysiology, and structural architecture of real tumors. Our ongoing efforts involve constructing heterotypic multicellular 3D tumor spheroids, serving as robust screening tools. This approach aims to enhance our understanding of nanodrugs penetration and accumulation within the tumor mass. By identifying key parameters, we strive to maximize therapeutic benefits. In an upcoming talk, I will share the most significant results from our research in this evolving field.