Based on the studies reported in the paper, the scientists draw several conclusions:
1) soft nanoparticles are able to persist in circulation in higher amounts at short times compared to hard nanoparticles, and this can be used to increase targeting to certain tissues;
2) at longer times, circulation differences between soft nanoparticles and hard nanoparticles are reduced;
3) this increased blood persistence can be attributed to the ability of softer particles to resist phagocytosis for longer times than their harder counterparts;
4) both soft and hard PEGDA hydrogel nanoparticles are eventually cleared by the spleen; and
5) harder particles are endocytosed much more rapidly and in higher amounts than softer nanoparticles, and this internalization trend is even more pronounced for immune cell phagocytosis.
By tuning elasticity, softer particles could be potentially utilized to avoid endocytosis and phagocytosis and effectively provide benefits in circulation and targeting by increasing opportunities to bind to target sites due to increased blood persistence.
However, if intracellular drug delivery or rapid cell internalization is desired, harder particles could be utilized to increase association with cells and increase particle uptake.
These results suggest that elasticity of nanoparticles can be leveraged to improve key drug delivery abilities of nanoparticles, and perhaps, elasticity can be best utilized in tandem with modifications of other physical (e.g., shape) and chemical (e.g., targeting ligands) parameters to create more advanced nanoparticle delivery systems.
Future studies will investigate the role that elasticity plays in both extravasation of nanoparticles through defects in endothelium and transcytosis through biological barriers.