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

Abstract

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 <i>in vivo</i> 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 <i>in vitro</i> cellular uptake, <i>in vivo</i> 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. <i>In vitro</i> 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. <i>In vivo</i> 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.