Comprehensive analysis of micro- and nanoparticle internalization in three-dimensional multicellular spheroids

Advancing our understanding of tussue/particles interaction basic biophysical processes, this study employs a multi-parameter analysis to explore the intricate interaction between multicellular spheroids representing model of normal and cancerous tissues and polymer particles with diverse properties. Through a comprehensive screening approach involving various cellular spheroids and polymeric particles differing in size, stiffness, and charge, we investigate the nuanced accumulation patterns of polymeric particles within 3d cellular models. We not only assess the ability of particles to accumulate in intracellular or intercellular spaces, but also identify specific areas in tissue models where they are present, such as proliferative, static, or necrotic areas. Utilizing the principles of principal components and machine learning algorithms, we pinpoint crucial factors influencing particles' cellular uptake within spheroids and elucidate parameters affecting their diffusion into distinct spheroid zones. This work underscores the potential of multi-parameter screenings in guiding the rational design of particles systems by identifying and characterizing key tissue interaction parameters.