Rapid Transport of Deformation-Tuned Nanoparticles across Biological Hydrogels and Cellular Barriers

Nanoparticle (NP) size, shape and surface charge have proven to affect the interaction of nanoparticles with cells and within animals. However, whether NP elasticity affects transport across various barriers outside and inside the cell remains elusive. Here, we experimentally and theoretically demonstrated that NPs with appropriate elasticity displayed superior mucus penetration and higher epithelial cellular uptake than their softer and harder counterparts in mucosal tissue. It is unprecedented that these semi-elastic NPs even displayed approximately 17-fold enhanced diffusivity than NPs with small size in mucus. Preliminary results further showed that semi-elastic NPs could effectively deliver the anticancer drug doxorubicin in rat orally. Molecular simulations and super-resolution microscopy revealed that the softer NPs deformed easily, which rendered them to accommodate with and adhere to the mucus fiber, thus showing the lowest permeation.