Tuning Nanoparticle Elasticity for Improved Biological Function

The physical and chemical attributes of nanoparticles have been systematically investigated to determine their role in key drug delivery processes such as circulation, targeting, and cellular uptake. These efforts have shown that physical modifications (e.g. tuning size or shape) can be used to influence the biological fate and function of nanoparticles and improve the drug delivery process. However, the role nanoparticle flexibility has on their biological function and fate has been less explored. As such, the potential benefits of tuning nanoparticle elasticity are not clear and similar systematic investigations are warranted. By synthesizing polyethylene glycol (PEG)-based hydrogel nanoparticles of uniform size (200 nm) with elastic moduli ranging from 0.255 kPa to 3000 kPa, we have investigated the role of particle elasticity on key functions including circulation time, tissue targeting, and cellular internalization. We show that softer nanoparticles (10 kPa) offer improved circulation and enhanced targeting compared to stiffer nanoparticles (3000 kPa) in vivo. In vitro studies showed that stiffer nanoparticles were internalized in significantly higher amounts than their softer counterparts in a variety of cell types. Tuning nanoparticle elasticity offers a new method to improve the circulation and targeting of nanoparticle drug delivery systems.