Molecular simulation of diffusion of rigidity-tuned nanoparticles in biological hydrogels

The penetration capability of drug nano-carriers (NCs) in biological hydrogels such, as mucus and tumor interstitial matrix, typically influence the efficiency of drug delivery. Therefore, understanding the effect of the physicochemical properties of drug carriers on their diffusion capability in biological hydrogels is important for the design and optimization of nano-carriers. Here, using a coarse-grained molecular dynamics model, we studied how the rigidity of NCs affected their diffusivity in biological hydrogels. The results showed that semi-elastic NCs have higher diffusivity than the hard and soft NCs. Furthermore, the affinity between the NCs and biological hydrogels and the size ratio between the hydrogel meshes and NCs also affect NC diffusivity. Further analysis revealed the mechanism that the deformation of the NCs dominates their diffusivity. These findings demonstrate that the rigidity of NCs is a key parameter in designing efficient NCs for deep penetration into biological hydrogels.