title: Improved targeting of ligand-modified adenovirus as a new near infrared fluorescence tumor imaging probe.
abstract: E1/E3-deleted Adenovirus 5 (Ad.5) possesses a great potential in gene therapy because of its high efficacy in gene transfer and low toxicity. Studies have shown that Coxsackie-Adenovirus receptor (CAR) is the determinant factor for the targeting of Adenovirus vectors. To extend the natural targeting of Ad to low CAR expressing tumors, we covalently attached folic acid (FA) to E1/E3-deleted Ad.5 capsids. Near-infrared (NIR) fluorescent dye ICG-Der-02 was subsequently conjugated with FA-Ad particles for in vivo imaging. The cell experiments and acute toxicity studies demonstrated the low toxicity of FA-Ad-ICG02 to normal cell/tissues. The dynamic behavior and targeting ability of FA-Ad-ICG02 to different tumors were investigated by NIR fluorescence imaging. In vitro and in vivo studies demonstrated its high targeting capability to CAR or FR positive tumors. The results support the potential of using ligand-modified Ad probe for tumor diagnosis and targeted therapy.
authors.affiliation: Department of Biomedical Engineering, School of Life Science and Technology, China Pharmaceutical University , Nanjing 210009, China.
authors.forename: Lingling
authors.initials: L
authors.lastname: Shan
authors.forename: Jianpeng
authors.initials: J
authors.lastname: Xue
authors.forename: Jing
authors.initials: J
authors.lastname: Guo
authors.forename: Zhiyu
authors.initials: Z
authors.lastname: Qian
authors.forename: Samuel
authors.initials: S
authors.lastname: Achilefu
authors.forename: Yueqing
authors.initials: Y
authors.lastname: Gu
mesh_terms: D000256:Adenoviridae / Q000737:chemistry*; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D005456:Fluorescent Dyes / Q000138:chemical synthesis / Q000737:chemistry*; D008024:Ligands; D015336:Molecular Probe Techniques; D015394:Molecular Structure; D009369:Neoplasms / Q000175:diagnosis*; D011991:Receptors, Virus / Q000032:analysis; D013050:Spectrometry, Fluorescence
chemical_list: D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D005456:Fluorescent Dyes; D008024:Ligands; D011991:Receptors, Virus