Time-resolved mapping of drug nanocarrier diffusion in biological media within microfluidic devices using synchrotron...

Nanomedicines have the potential to enhance the efficacy of current cancer therapies while minimizing adverse effects. Their transport through the tumor interstitium is critical for their therapeutic outcome and clinical success. However, how nanomedicines move through complex biological environments remains poorly understood. This gap limits the ability to reliably predict their therapeutic outcome, ultimately hampering their clinical translation. Characterization of the nanomedicine's diffusive transport remains challenging due to the complexities associated with time-resolved detection. Fluorescence-based detection techniques generally require tagging the nanocarriers, which may alter their transport properties. Thus, innovative approaches are required to accurately predict the transport properties of nanomedicines across biological barriers without modifying them. In this work, we present a label-free strategy that combines synchrotron X-ray fluorescence imaging and microfluidic devices to track nanomedicine diffusion in biologically relevant environments with high temporal and spatial resolution. The diffusive penetration of Au and Fe-Au-based nanocarriers into an extracellular hydrogel matrix was studied, and their diffusion coefficients were successfully determined. Differences in transport behavior emerged for nanoparticles differing in hydrodynamic sizes and ζ-potential, demonstrating this technique's potential to provide a reliable and versatile methodology to investigate nanomedicine transport processes in complex biological matrices.