title: In vivo fate tracking of degradable nanoparticles for lung gene transfer using PET and Ĉerenkov imaging.
abstract: Nanoparticles (NPs) play expanding roles in biomedical applications including imaging and therapy, however, their long-term fate and clearance profiles have yet to be fully characterized in vivo. NP delivery via the airway is particularly challenging, as the clearance may be inefficient and lung immune responses complex. Thus, specific material design is required for cargo delivery and quantitative, noninvasive methods are needed to characterize NP pharmacokinetics. Here, biocompatible poly(acrylamidoethylamine)-b-poly(dl-lactide) block copolymer-based degradable, cationic, shell-cross-linked knedel-like NPs (Dg-cSCKs) were employed to transfect plasmid DNA. Radioactive and optical beacons were attached to monitor biodistribution and imaging. The preferential release of cargo in acidic conditions provided enhanced transfection efficiency compared to non-degradable counterparts. In vivo gene transfer to the lung was correlated with NP pharmacokinetics by radiolabeling Dg-cSCKs and performing quantitative biodistribution with parallel positron emission tomography and Čerenkov imaging. Quantitation of imaging over 14 days corresponded with the pharmacokinetics of NP movement from the lung to gastrointestinal and renal routes, consistent with predicted degradation and excretion. This ability to noninvasively and accurately track NP fate highlights the advantage of incorporating multifunctionality into particle design.
authors.affiliation: Department of Radiology, Washington University, St. Louis, MO 63110, USA.
authors.forename: Kvar C L
authors.initials: KC
authors.lastname: Black
authors.affiliation: Department of Internal Medicine, Washington University, St. Louis, MO 63110, USA.
authors.forename: Aida
authors.initials: A
authors.lastname: Ibricevic
authors.affiliation: Department of Internal Medicine, Washington University, St. Louis, MO 63110, USA.
authors.forename: Sean P
authors.initials: SP
authors.lastname: Gunsten
authors.affiliation: Department of Chemistry, Texas A&M University, College Station, TX 77843, USA; Department of Chemical Engineering, Texas A&M University, College Station, TX 77843, USA.
authors.forename: Jeniree A
authors.initials: JA
authors.lastname: Flores
authors.affiliation: Department of Chemistry, Texas A&M University, College Station, TX 77843, USA; Department of Chemical Engineering, Texas A&M University, College Station, TX 77843, USA.
authors.forename: Tiffany P
authors.initials: TP
authors.lastname: Gustafson
authors.affiliation: Department of Chemistry, Texas A&M University, College Station, TX 77843, USA; Department of Chemical Engineering, Texas A&M University, College Station, TX 77843, USA; Laboratory for Synthetic-Biologic Interactions, Texas A&M University, College Station, TX 77843, USA.
authors.forename: Jeffery E
authors.initials: JE
authors.lastname: Raymond
authors.affiliation: Department of Chemistry, Texas A&M University, College Station, TX 77843, USA.
authors.forename: Sandani
authors.initials: S
authors.lastname: Samarajeewa
authors.affiliation: Department of Chemistry, Texas A&M University, College Station, TX 77843, USA.
authors.forename: Ritu
authors.initials: R
authors.lastname: Shrestha
authors.affiliation: Department of Chemistry, Texas A&M University, College Station, TX 77843, USA.
authors.forename: Simcha E
authors.initials: SE
authors.lastname: Felder
authors.affiliation: Department of Internal Medicine, Washington University, St. Louis, MO 63110, USA.
authors.forename: Tianyi
authors.initials: T
authors.lastname: Cai
authors.affiliation: Department of Chemistry, Washington University, St. Louis, MO 63110, USA.
authors.forename: Yuefei
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Department of Internal Medicine, Washington University, St. Louis, MO 63110, USA.
authors.forename: Ann-Kathrin
authors.initials: AK
authors.lastname: Löbs
authors.affiliation: Department of Radiology, Washington University, St. Louis, MO 63110, USA.
authors.forename: Natalia
authors.initials: N
authors.lastname: Zhegalova
authors.affiliation: Department of Radiology, Washington University, St. Louis, MO 63110, USA.
authors.forename: Deborah H
authors.initials: DH
authors.lastname: Sultan
authors.affiliation: Department of Radiology, Washington University, St. Louis, MO 63110, USA.
authors.forename: Mikhail
authors.initials: M
authors.lastname: Berezin
authors.affiliation: Department of Chemistry, Texas A&M University, College Station, TX 77843, USA; Department of Chemical Engineering, Texas A&M University, College Station, TX 77843, USA; Laboratory for Synthetic-Biologic Interactions, Texas A&M University, College Station, TX 77843, USA.
authors.forename: Karen L
authors.initials: KL
authors.lastname: Wooley
authors.affiliation: Department of Radiology, Washington University, St. Louis, MO 63110, USA.
authors.forename: Yongjian
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Radiology, Washington University, St. Louis, MO 63110, USA; Department of Internal Medicine, Washington University, St. Louis, MO 63110, USA. Electronic address: brodys@wustl.edu.
authors.forename: Steven L
authors.initials: SL
authors.lastname: Brody
mesh_terms: D000818:Animals; D004247:DNA / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007457:Iodine Radioisotopes; D049449:Luminescence; D008168:Lung / Q000378:metabolism*; D051379:Mice; D064847:Multimodal Imaging; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010957:Plasmids / Q000378:metabolism; D049268:Positron-Emission Tomography; D012996:Solutions; D014018:Tissue Distribution; D014162:Transfection / Q000379:methods*
chemical_list: D007457:Iodine Radioisotopes; D012996:Solutions; D004247:DNA
keywords: Biodistribution; Cytotoxicity; Degradable nanoparticle; Gene expression; Lung; Čerenkov luminescence imaging