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 MONs 0 -HA, semi-elastic MONs 20 -HA and MONs 50 -HA, elastic MONs 100 -HA and MONs 200 -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 MONs 100 -HA and MONs 200 -HA (0.4 and 0.29 GPa) exhibit significantly greater cellular uptake relative to semi-elastic MONs 20 -HA and MONs 50 -HA (0.93 and 0.78 GPa) or rigid MONs 0 -HA (1.64 GPa). Simultaneously, these elastic MONs 100 -HA and MONs 200 -HA show an efficiently prolonged circulation time. In vivo results revealed that the elastic MONs 100 -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.