Elasticity of mesoporous nanocapsules regulates cellular uptake, blood circulation, and intratumoral distribution

The elasticity of nanoparticles plays a critical role in regulating nanoparticle-biosystem interactions. However, the elasticity of traditional organic-based carriers can only be regulated within a narrow range, and the effects of elasticity on in vivo biological processes have not been evaluated until now. Here, we construct hyaluronic acid modified mesoporous organosilica nanoparticles (MONs-HA) with a wide range of elasticity by an interior preferential etching approach and investigate the impact of their elasticity on in vitro cellular uptake, in vivo blood circulation, and tumor accumulation. The Young's moduli of the prepared MONs-HA are 1.64, 0.93, 0.78, 0.4 and 0.29 GPa (denoted as rigid MONs₀-HA, semi-elastic MONs₂₀-HA and MONs₅₀-HA, elastic MONs₁₀₀-HA and MONs₂₀₀-HA), respectively. They all possess a similar hydrodynamic size (245-257 nm), similar surface electronegativity (-27 to -35 mV), and excellent dispersibility. In vitro experiments demonstrate that the elastic MONs₁₀₀-HA and MONs₂₀₀-HA (0.4 and 0.29 GPa) exhibit significantly greater cellular uptake relative to semi-elastic MONs₂₀-HA and MONs₅₀-HA (0.93 and 0.78 GPa) or rigid MONs₀-HA (1.64 GPa). Simultaneously, these elastic MONs₁₀₀-HA and MONs₂₀₀-HA show an efficiently prolonged circulation time. In vivo results revealed that the elastic MONs₁₀₀-HA show enhanced tumor accumulation compared to semi-elastic and rigid MONs-HA after intravenous administration. These desirable features of elasticity can direct the design of nanoplatforms, leading to an enhanced tumor delivery efficiency.