The role of substrate topography on the cellular uptake of nanoparticles.
Improving targeting efficacy has been a central focus of the studies on nanoparticle (NP)-based drug delivery nanocarriers over the past decades. As cells actively sense and respond to the local physical environments, not only the NP design (e.g., size, shape, ligand density, etc.) but also the cell mechanics (e.g., stiffness, spreading, expressed receptors, etc.) affect the cellular uptake efficiency. While much work has been done to elucidate the roles of NP design for cells seeded on a flat tissue culture surface, how the local physical environments of cells mediate uptake of NPs remains unexplored, despite the widely known effect of local physical environments on cellular responses in vitro and disease states in vivo. Here, we report the active responses of human osteosarcoma cells to fibrous substrate topographies and the subsequent changes in the cellular uptake of NPs. Our experiments demonstrate that surface topography modulates cellular uptake efficacy by mediating cell spreading and membrane mechanics. The findings provide a concrete example of the regulative role of the physical environments of cells on cellular uptake of NPs, therefore advancing the rational design of NPs for enhanced drug delivery in targeted cancer therapy.
Department of Engineering Science and Mechanics, The Pennsylvania State University, University Park, Pennsylvania, 16802.
Changjin
C
Huang
Department of Bioengineering, The Pennsylvania State University, University Park, Pennsylvania, 16802.
Tugba
T
Ozdemir
Department of Surgery, The Pennsylvania State University, College of Medicine, Hershey, Pennsylvania, 17033.
Li-Chong
LC
Xu
Department of Bioengineering, The Pennsylvania State University, University Park, Pennsylvania, 16802.
Peter J
PJ
Butler
Department of Bioengineering, The Pennsylvania State University, University Park, Pennsylvania, 16802.|Department of Surgery, The Pennsylvania State University, College of Medicine, Hershey, Pennsylvania, 17033.
Christopher A
CA
Siedlecki
Department of Bioengineering, The Pennsylvania State University, University Park, Pennsylvania, 16802.
Justin L
JL
Brown
Department of Engineering Science and Mechanics, The Pennsylvania State University, University Park, Pennsylvania, 16802.|Department of Bioengineering, The Pennsylvania State University, University Park, Pennsylvania, 16802.
Sulin
S
Zhang
D045744:Cell Line, Tumor; D004337:Drug Carriers / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D006801:Humans; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D013499:Surface Properties
D004337:Drug Carriers
endocytosis; fibers; nanoparticles; scaffolds; topographies