Effect of Elasticity of Silica Capsules on Cellular Uptake.

Understanding the impact of the physicochemical properties of nanoparticles (NPs) on cellular uptake is important to design optimal drug-delivery nanocarriers. Therein, the influence of NP elasticity on bio-nano-interactions remains elusive due to the complexity of factors affecting cellular uptake. Herein, we synthesized SiO2 capsules with tunable elasticity using metal-organic frameworks as templates to investigate their interactions with cells. Young's moduli of the resultant water-filled SiO2 capsules with identical size, shape, composition, and surface charge can be controlled from 3.8 MPa to 4.7 GPa via the variation of capsule shell thickness. As a result, increased elasticity of SiO2 capsules results in higher cellular uptake. Stiff SiO2 capsules have almost 9 times as much cellular uptake as the soft ones. In addition, the elasticity of SiO2 capsules influences cellular uptake pathways, where the clathrin-mediated pathway is preferred for stiff capsules while the uptake of the soft capsules is mostly mediated by a caveolae-dependent pathway. This work confirms the important role of NP elasticity in nonspecific cell interactions, which can provide a foundational understanding for engineering drug-delivery nanocarriers.