Many diseases are characterized by nanostructural changes in connective fibers and soluble proteins, which can indicate or drive disease progression. Noninvasive methods sensitive to nanotopological changes in 3D tissue models can elucidate biophysical changes associated with disease progression. Nanoparticles probe their environment via their diffusion, which is impacted by the size and connectivity of pores into which they freely diffuse. Here, we show that optical coherence tomography provides depth-resolved imaging of gold nanorods (GNRs) to infer local biological nanotopology. We demonstrate the broad potential of this method by sensing changes in diffusion of GNRs in 3D models of mammary ECM and pulmonary mucus
