title: TIPS pentacene loaded PEO-PDLLA core-shell nanoparticles have similar cellular uptake dynamics in M1 and M2 macrophages and in corresponding in vivo microenvironments.
abstract: Nanoparticle based drug delivery platforms have the potential to transform disease treatment paradigms and therapeutic strategies, especially in the context of pulmonary medicine. Once administered, nanoparticles disperse throughout the lung and many are phagocytosed by macrophages. However, there is a paucity of knowledge regarding cellular up-take dynamics of nanoparticles due largely to macrophage heterogeneity. To address this issue, we sought to better define nanoparticle up-take using polarized M1 and M2 macrophages and novel TIPS-pentacene loaded PEO-PDLLA nanoparticles. Our data reveal that primary macrophages polarized to either M1 or M2 phenotypes have similar levels of nanoparticle phagocytosis. Similarly, M1 and M2 polarized macrophages isolated from the lungs of mice following either acute (Th1) or allergic (Th2) airway inflammation also demonstrated equivalent levels of nanoparticle up-take. Together, these studies provide critical benchmark information pertaining to cellular up-take dynamics and biodistribution of nanoparticles in the context of clinically relevant inflammatory microenvironments.
authors.affiliation: Department of Biomedical Sciences and Pathobiology, VA-MD College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, USA.
authors.forename: Dylan K
authors.initials: DK
authors.lastname: McDaniel
authors.affiliation: Department of Chemical Engineering, Virginia Tech, Blacksburg, VA, USA.
authors.forename: Ami
authors.initials: A
authors.lastname: Jo
authors.affiliation: Graduate Program in Translational Biology, Medicine and Health, Virginia Tech, Blacksburg, VA, USA.
authors.forename: Veronica M
authors.initials: VM
authors.lastname: Ringel-Scaia
authors.affiliation: Department of Biomedical Sciences and Pathobiology, VA-MD College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, USA.
authors.forename: Sheryl
authors.initials: S
authors.lastname: Coutermarsh-Ott
authors.affiliation: Department of Biomedical Sciences and Pathobiology, VA-MD College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, USA.
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Rothschild
authors.affiliation: Graduate Program in Translational Biology, Medicine and Health, Virginia Tech, Blacksburg, VA, USA.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Powell
authors.affiliation: Department of Chemistry, Virginia Tech, Blacksburg, VA, USA; Macromolecules Innovation Institute, Virginia Tech, Blacksburg, VA, USA.
authors.forename: Rui
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Department of Chemistry, Virginia Tech, Blacksburg, VA, USA; Macromolecules Innovation Institute, Virginia Tech, Blacksburg, VA, USA.
authors.forename: Timothy E
authors.initials: TE
authors.lastname: Long
authors.affiliation: Department of Biomedical Sciences and Pathobiology, VA-MD College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, USA; Graduate Program in Translational Biology, Medicine and Health, Virginia Tech, Blacksburg, VA, USA.
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Oestreich
authors.affiliation: Department of Chemistry, Virginia Tech, Blacksburg, VA, USA; Macromolecules Innovation Institute, Virginia Tech, Blacksburg, VA, USA.
authors.forename: Judy S
authors.initials: JS
authors.lastname: Riffle
authors.affiliation: Department of Chemical Engineering, Virginia Tech, Blacksburg, VA, USA; Graduate Program in Translational Biology, Medicine and Health, Virginia Tech, Blacksburg, VA, USA; Macromolecules Innovation Institute, Virginia Tech, Blacksburg, VA, USA.
authors.forename: Richey M
authors.initials: RM
authors.lastname: Davis
authors.affiliation: Department of Biomedical Sciences and Pathobiology, VA-MD College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, USA; Graduate Program in Translational Biology, Medicine and Health, Virginia Tech, Blacksburg, VA, USA; Macromolecules Innovation Institute, Virginia Tech, Blacksburg, VA, USA. Electronic address: icallen@vt.edu.
authors.forename: Irving C
authors.initials: IC
authors.lastname: Allen
mesh_terms: D000818:Animals; D001249:Asthma; D002478:Cells, Cultured; D004337:Drug Carriers / Q000737:chemistry / Q000378:metabolism*; D004852:Epoxy Compounds / Q000737:chemistry / Q000378:metabolism*; D008168:Lung / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000737:chemistry / Q000378:metabolism*; D017646:Organosilicon Compounds / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D011091:Polyesters / Q000737:chemistry / Q000378:metabolism*; D014018:Tissue Distribution
chemical_list: D004337:Drug Carriers; D004852:Epoxy Compounds; D017646:Organosilicon Compounds; C402662:PEO-poly(lactide); D011091:Polyesters; C522282:bis(triisopropylsilylethynyl)pentacene
keywords: Asthma; Inflammation; LPS; Nanoparticle; Pulmonary drug delivery