title: Unique size and shape-dependent uptake behaviors of non-spherical nanoparticles by endothelial cells due to a shearing flow.
abstract: The size and shape of nanoparticle (NP) drug carriers can potentially be manipulated to increase the drug delivery efficacy because of their effects on particle margination and interactions with various cells in vivo. It is found in this work that the presence of a physiologically relevant shearing flow rate results in very different size and shape-dependent uptake behavior of negatively charged, non-spherical polyethylene glycol (PEG) hydrogel NPs by endothelial cells (ECs) cultured in a microchannel compared to uptake of either identical NPs in static culture or spherical particles in a shear flow. In particular, larger rod- and disk-shaped PEG NPs show more uptake than smaller ones, opposite to the size effect observed for spherical particles in a flow. Moreover, the trend observed in this dynamic uptake experiment also differs from that reported for uptake of similar PEG NPs by ECs in a static culture, where the smaller disks were found to be uptaken the most. These differences suggest that the increasing rotational and tumbling motions of larger-size non-spherical NPs in the flow play a dominant role in NP margination and cell interaction, compared to Brownian motion, gravity, and cell membrane deformation energy. These findings suggest that the coupling between NP geometry and shear flow is an important factor that needs to be accounted for in the design of the size and shape of nanocarriers.
authors.affiliation: Department of Mechanical Engineering, The University of Texas at Austin, Austin, TX 78712-1591, United States. Electronic address: Jurney4@gmail.com.
authors.forename: Patrick
authors.initials: P
authors.lastname: Jurney
authors.affiliation: Department of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA 30332-0535, United States. Electronic address: rachit.agarwal@me.gatech.edu.
authors.forename: Rachit
authors.initials: R
authors.lastname: Agarwal
authors.affiliation: Department of Mechanical Engineering, The University of Texas at Austin, Austin, TX 78712-1591, United States. Electronic address: vsingh@militho.com.
authors.forename: Vikramjit
authors.initials: V
authors.lastname: Singh
authors.affiliation: Department of Mechanical Engineering, The University of Texas at Austin, Austin, TX 78712-1591, United States. Electronic address: davidchoi@utexas.edu.
authors.forename: David
authors.initials: D
authors.lastname: Choi
authors.affiliation: Department of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA 30332-0535, United States. Electronic address: krish.roy@gatech.edu.
authors.forename: Krishnendu
authors.initials: K
authors.lastname: Roy
authors.affiliation: Department of Mechanical Engineering, The University of Texas at Austin, Austin, TX 78712-1591, United States. Electronic address: sv.sreeni@mail.utexas.edu.
authors.forename: S V
authors.initials: SV
authors.lastname: Sreenivasan
authors.affiliation: Department of Mechanical Engineering, The University of Texas at Austin, Austin, TX 78712-1591, United States. Electronic address: lishi@mail.utexas.edu.
authors.forename: Li
authors.initials: L
authors.lastname: Shi
mesh_terms: D002478:Cells, Cultured; D016650:Fluorescein-5-isothiocyanate / Q000008:administration & dosage; D005456:Fluorescent Dyes / Q000008:administration & dosage; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism*; D006801:Humans; D055595:Mechanical Phenomena; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D010316:Particle Size; D011092:Polyethylene Glycols / Q000008:administration & dosage
chemical_list: D005456:Fluorescent Dyes; D011092:Polyethylene Glycols; D016650:Fluorescein-5-isothiocyanate
keywords: Endothelial cell culture; Nanoparticle drug delivery; Nanoparticle shape; Shear stress