Using elasticity to control biological transport and delivery of polymer nanogels

Matthew Helgeson, Chemical Engineering, University of California, Santa Barbara, Santa Barbara, CA, USA
Mengwen Zhang, Chemical Engineering, University Of California, Santa Barbara
Maksymilian Nowak, Chemical Engineering, University Of California, Santa Barbara
Aaron Anselmo, Chemical Engineering, University Of California, Santa Barbara
Samir Mitragotri, Chemical Engineering, University Of California, Santa Barbara



The ability of matrix or substrate elasticity to significantly impact the differentiation and growth of biological cells and tissues is well-established, and has resulted in a number of advances in biomaterials for medical applications. However, the impact such elasticity-mediated interactions might have on various aspects of nanomedicine, i.e. the use of nanoparticles to deliver therapeutic or diagnostic species, is largely unknown. To better understand the possible impact of nanoparticle elasticity on nanoparticle delivery, we have developed new colloidal syntheses to control nanoparticle elasticity, and utilized them to systematically study its effects on various biological transport processes. Specifically, novel nanoemulsion templating methods allow for the creation of a series of polyethylene glycol (PEG)-based hydrogel nanoparticles of uniform size and surface charge density with elastic moduli ranging from soft (~0.2 kPa) to hard (3 MPa) relative to biological tissues. We use them to investigate the role of particle elasticity on key biological transport processes including blood circulation, biodistribution, antibody-mediated targeting, endocytosis and phagocytosis. The results demonstrate that softer nanoparticles offer enhanced circulation and subsequently enhanced targeting compared to harder nanoparticles in vivo. Furthermore, in vitro experiments show that softer nanoparticles exhibit significantly reduced cellular uptake to a range of disease-relevant cell types. Thus, tuning nanoparticle elasticity offers a potential route to improve biological fate of nanoparticles. Eventually, we extend the nanoemulsion templating methods to demonstrate the encapsulation of molecular and colloidal cargoes within the soft nanogels, providing new capabilities for nanomedicine.