Single-cell resolution of nanoparticle uptake and release: quantitative frameworks for targeted therapy

Nanoparticle-based delivery systems are redefining precision medicine by enabling targeted transport and controlled release of therapeutic cargos. Yet, their clinical translation hinges on an in-depth understanding of uptake dynamics, intracellular trafficking, and release mechanisms at the single-cell level. This review represents a brief overview of the mechanistic insights of nano-bio interactions in single cells and highlights the recent advances in quantitative tools to understand these processes with unprecedented resolution. We describe the potential of the five core instrumental techniques for these studies, including confocal microscopy (CLSM), two-photon microscopy, X-ray fluorescence microscopy (XRF), flow cytometry, and inductively coupled plasma mass spectrometry (ICP-MS). By advancing quantitative single-cell analytics, these approaches pave the way for the design of safer and more effective nanomedicine.