title: PEG conjugation of a near-infrared fluorescent probe for noninvasive dual imaging of lung deposition and gene expression by pulmonary gene delivery.
abstract: Dual imaging of lung deposition and gene expression following the pulmonary delivery of a gene formulation is useful for a precise analysis of gene transfection efficiency in vivo. As a novel probe for evaluating lung deposition, in this study, a poly(ethylene glycol)-conjugated near-infrared fluorescent probe (PEG-NIRF) was newly synthesized, and compared with indocyanine green (ICG), for application to pDNA/polyethyleneimine (PEI) complex. PEG-NIRF had superior characteristics including a larger Stokes shift (absorption maximum, 662 nm; emission maximum, 772 nm) and relatively equivalent fluorescence intensity compared with ICG. ICG affected the physicochemical properties of pDNA/PEI complex with a loss of fluorescence intensity, while PEG-NIRF did not. Experiments in mice demonstrated that PEG-NIRF showed greater lung localization than ICG following pulmonary co-delivery with pDNA/PEI complex, indicating the possibility of accurately evaluating lung deposition. Moreover, it was clarified that the evaluation of lung deposition by PEG-NIRF even at 60 min could be significantly correlated with gene expression in each mouse following pulmonary co-delivery with pDNA/PEI complex. These results suggest that PEG-NIRF is widely applicable to the dual imaging of the lung deposition and gene expression of inhaled gene formulations.
authors.affiliation: Faculty of Pharmacy, Meijo University, Nagoya, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Okuda
authors.forename: Yuko
authors.initials: Y
authors.lastname: Kobayashi
authors.forename: Shinya
authors.initials: S
authors.lastname: Yanamoto
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Okamoto
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D004396:Coloring Agents / Q000737:chemistry / Q000493:pharmacokinetics; D004247:DNA / Q000008:administration & dosage*; D005260:Female; D005456:Fluorescent Dyes / Q000737:chemistry* / Q000493:pharmacokinetics; D015870:Gene Expression; D018014:Gene Transfer Techniques; D007097:Imines / Q000737:chemistry / Q000493:pharmacokinetics; D007208:Indocyanine Green / Q000737:chemistry / Q000493:pharmacokinetics; D007259:Infrared Rays; D008168:Lung / Q000378:metabolism*; D051379:Mice; D008813:Mice, Inbred ICR; D010957:Plasmids; D011092:Polyethylene Glycols / Q000737:chemistry* / Q000493:pharmacokinetics; D011095:Polyethylenes / Q000737:chemistry / Q000493:pharmacokinetics; D013997:Time Factors; D014162:Transfection / Q000379:methods
chemical_list: D004396:Coloring Agents; D005456:Fluorescent Dyes; D007097:Imines; D011095:Polyethylenes; C505405:poly(ethylene imine); D011092:Polyethylene Glycols; D004247:DNA; D007208:Indocyanine Green