The impact of hydrogel matrix elasticity is known to significantly impact the differentiation and growth of biological cells and tissues. Much less studied, however, is the impact elasticity of nanoparticles has on the circulation and organ or cellular targeting, such that the potential benefits of tuning nanoparticle elasticity are not clear. Here, we describe a method to synthesize a series polyethylene glycol (PEG)-based hydrogel nanoparticles of uniform size and surface charge density with elastic moduli ranging from very soft (~0.2 kPa) to very hard (3 MPa). These particles possess well-characterized microstructure and exhibit low toxicity compared to other nanoparticle vehicles, and are thus well-suited to investigating the role of particle elasticity on key biological transport processes including blood circulation, biodistribution, antibody-mediated targeting, endocytosis and phagocytosis. Our results demonstrate that softer nanoparticles offer enhanced circulation and subsequently enhanced targeting compared to harder nanoparticles <i>in vivo</i>. Furthermore, <i>in vitro</i> experiments show that softer nanoparticles exhibit significantly reduced cellular uptake in immune cells (J774 macrophages), endothelial cells (bEnd.3) and cancer cells (4T1). Tuning nanoparticle elasticity potentially offers a method to improve biological fate of nanoparticles by offering enhanced circulation, reduced immune system uptake and improved targeting.

Using elasticity to control biological transport of polymer nanogels

251st National Meeting (2016)

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