title: Elasticity of nanoparticles influences their blood circulation, phagocytosis, endocytosis, and targeting.
abstract: The impact of physical and chemical modifications of nanoparticles on their biological function has been systemically investigated and exploited to improve their circulation and targeting. However, the impact of nanoparticles' flexibility (i.e., elastic modulus) on their function has been explored to a far lesser extent, and the potential benefits of tuning nanoparticle elasticity are not clear. Here, we describe a method to synthesize polyethylene glycol (PEG)-based hydrogel nanoparticles of uniform size (200 nm) with elastic moduli ranging from 0.255 to 3000 kPa. These particles are used to investigate the role of particle elasticity on key functions including blood circulation time, biodistribution, antibody-mediated targeting, endocytosis, and phagocytosis. Our results demonstrate that softer nanoparticles (10 kPa) offer enhanced circulation and subsequently enhanced targeting compared to harder nanoparticles (3000 kPa) in vivo. Furthermore, in vitro 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 the biological fate of nanoparticles by offering enhanced circulation, reduced immune system uptake, and improved targeting.
authors.affiliation: Department of Chemical Engineering, Center for Bioengineering, University of California, Santa Barbara, California 93106, United States.
authors.forename: Aaron C
authors.initials: AC
authors.lastname: Anselmo
authors.affiliation: Department of Chemical Engineering, Center for Bioengineering, University of California, Santa Barbara, California 93106, United States.
authors.forename: Mengwen
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Chemical Engineering, Center for Bioengineering, University of California, Santa Barbara, California 93106, United States.
authors.forename: Sunny
authors.initials: S
authors.lastname: Kumar
authors.affiliation: Department of Chemical Engineering, Center for Bioengineering, University of California, Santa Barbara, California 93106, United States.
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Vogus
authors.affiliation: Department of Chemical Engineering, Center for Bioengineering, University of California, Santa Barbara, California 93106, United States.
authors.forename: Stefano
authors.initials: S
authors.lastname: Menegatti
authors.affiliation: Department of Chemical Engineering, Center for Bioengineering, University of California, Santa Barbara, California 93106, United States.
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Helgeson
authors.affiliation: Department of Chemical Engineering, Center for Bioengineering, University of California, Santa Barbara, California 93106, United States.
authors.forename: Samir
authors.initials: S
authors.lastname: Mitragotri
mesh_terms: D000818:Animals; D001769:Blood / Q000378:metabolism*; D045744:Cell Line, Tumor; D055119:Elastic Modulus; D006801:Humans; D020100:Hydrogels / Q000737:chemistry* / Q000378:metabolism* / Q000493:pharmacokinetics; D051379:Mice; D053758:Nanoparticles; D010316:Particle Size; D010587:Phagocytosis; D011092:Polyethylene Glycols / Q000737:chemistry; D013329:Structure-Activity Relationship; D014018:Tissue Distribution
chemical_list: D020100:Hydrogels; D011092:Polyethylene Glycols
keywords: biodistribution; circulation; elasticity; nanoemulsion; nanogel; nanomedicine; nanoparticles; targeting