title: Effect of shape, size, and aspect ratio on nanoparticle penetration and distribution inside solid tissues using 3D spheroid models.
abstract: Efficient penetration and uniform distribution of nanoparticles (NPs) inside solid tissues and tumors is paramount to their therapeutic and diagnostic success. While many studies have reported the effect of NP size and charge on intratissue distribution, role of shape, and aspect ratio on NP transport inside solid tissues remain unclear. Here experimental and theoretical studies are reported on how nanoscale geometry of Jet and Flash Imprint Lithography-fabricated, polyethylene-glycol-based anionic nanohydrogels affect their penetration and distribution inside 3D spheroids, a model representing the intervascular region of solid, tumor-like tissues. Unexpectedly, low aspect ratio cylindrical NPs (H/D ≈0.3; disk-like particles, 100 nm height, and 325 nm diameter) show maximal intratissue delivery (>50% increase in total cargo delivered) and more uniform penetration compared to nanorods or smaller NPs of the same shape. This is in contrast to spherical NPs where smaller NP size resulted in deeper, more uniform penetration. Our results provide fundamental new knowledge on NP transport inside solid tissues and further establish shape and aspect ratio as important design parameters in developing more efficient, better penetrating, nanocarriers for drug, or contrast-agent delivery.
authors.affiliation: The Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA, 30332, USA.
authors.forename: Rachit
authors.initials: R
authors.lastname: Agarwal
authors.affiliation: Department of Mechanical EngineeringThe University of Texas at Austin, Austin, TX, 78712, USA.
authors.forename: Patrick
authors.initials: P
authors.lastname: Jurney
authors.affiliation: Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX, 78712, USA.
authors.forename: Mansi
authors.initials: M
authors.lastname: Raythatha
authors.affiliation: Department of Mechanical EngineeringThe University of Texas at Austin, Austin, TX, 78712, USA.
authors.forename: Vikramjit
authors.initials: V
authors.lastname: Singh
authors.affiliation: Department of Mechanical EngineeringThe University of Texas at Austin, Austin, TX, 78712, USA.
authors.forename: Sidlgata V
authors.initials: SV
authors.lastname: Sreenivasan
authors.affiliation: Department of Mechanical EngineeringThe University of Texas at Austin, Austin, TX, 78712, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Shi
authors.affiliation: The Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University, Georgia Institute of Technology, Atlanta, GA, 30332, USA.
authors.forename: Krishnendu
authors.initials: K
authors.lastname: Roy
mesh_terms: D057809:HEK293 Cells; D006801:Humans; D008958:Models, Molecular; D054802:Molecular Imprinting; D053758:Nanoparticles / Q000737:chemistry*; D043942:Nanotubes / Q000737:chemistry; D009369:Neoplasms / Q000188:drug therapy; D011092:Polyethylene Glycols / Q000737:chemistry; D018874:Spheroids, Cellular / Q000187:drug effects* / Q000378:metabolism
chemical_list: D011092:Polyethylene Glycols
keywords: nanodisks; nanoparticle shape; nanorods; spheroids; tumor distribution