Understanding the diffusive transport of nanoparticles in agarose hydrogels

Abstract

The enhanced delivery of nanoparticle (NP) drugs in the human system is a revolutionary approach for various diseases, e.g., cancer therapy, in which nanoparticle diffusion is one of the main routes of transport. The diffusive transport of nanoparticles in complex tumor microenvironments is intriguing, while its complete understanding is still nascent. Herein, we experimentally report a systematic study of nanoparticle diffusion in model porous media, i.e., agarose (AG) hydrogels. By examining both the time-averaged and ensemble-averaged mean square displacements (MSDs), the heterogeneous and spatially dependent mobility, as well as the significant hydrodynamic damping effect, are identified. The concept of ergodicity breaking (EB) is employed and correlated with the measured non-Gaussian displacement probability distributions (DPDs). The non-Gaussian profile is clarified to be attributed to the superposition of the coexisted Gaussian and non-Gaussian motions of the individual nanoparticles. Furthermore, the interstitial viscosity is found to only affect the probed heterogeneity temporarily but never modify the intrinsic non-ergodicity of the porous media. Our results give a comprehensive understanding of anomalous diffusion in spatially heterogeneous porous media and could provide the imperative knowledge to improve drug delivery in physiological media.