title: Fate of Organic Functionalities Conjugated to Theranostic Nanoparticles upon Their Activation.
abstract: Neutron activation is widely applied for the preparation of radioactive isotopes to be used in imaging and/or therapy. The type of diagnostic/therapeutic agents varies from small chelates coordinating radioactive metal ions to complex nanoparticulate systems. Design of these agents often relies on conjugation of certain organic functionalities that determine their pharmacokinetics, biodistribution, targeting, and cell-penetrating abilities, or simply on tagging them with an optical label. The conjugation chemistry at the surface of nanoparticles and their final purification often require laborious procedures that become even more troublesome when radioactive materials are involved. This study represents a thorough investigation on the effects of neutron activation on the organic moieties of functionalized nanoparticles, with special focus on (166)Ho2O3 particles conjugated with PEG-fluorescein and PEG-polyarginine motives. Spectroscopic and thermogravimetric analyses demonstrate only a limited degradation of PEG-fluorescein upon irradiation of the particles up to 10 h using a thermal neutron flux of 5 × 10(16) m(-2) s(-1). Cell experiments show that the polyarginine-based mechanisms of membrane penetration remain unaltered after exposure of the functionalized particles to the mixed field of neutrons and gammas present during activation. This confirms that radiation damage on the PEG-polyarginines is minimal. Intrinsic radiations from (166)Ho do not seem to affect the integrity of conjugated organic material. These findings open up a new perspective to simplify the procedures for the preparation of functionalized metal-based nanosystems that need to be activated by neutron irradiation in order to be applied for diagnostic and/or therapeutic purposes.
authors.affiliation: Department of Biotechnology, Delft University of Technology , Julianalaan 136, 2628 BL Delft, The Netherlands.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Martinelli
authors.affiliation: Radiation Science and Technology, Delft University of Technology , Mekelweg 15, 2629 JB Delft, The Netherlands.
authors.forename: Antonia G
authors.initials: AG
authors.lastname: Denkova
authors.affiliation: Radiation Science and Technology, Delft University of Technology , Mekelweg 15, 2629 JB Delft, The Netherlands.|Institut Charles Sadron (CNRS) , 23 Rue du Loess, 67034 Strasbourg, France.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Arranja
authors.affiliation: Radiation Science and Technology, Delft University of Technology , Mekelweg 15, 2629 JB Delft, The Netherlands.
authors.forename: Baukje E
authors.initials: BE
authors.lastname: Terpstra
authors.affiliation: Department of Biotechnology, Delft University of Technology , Julianalaan 136, 2628 BL Delft, The Netherlands.
authors.forename: Wuyuan
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Biotechnology, Delft University of Technology , Julianalaan 136, 2628 BL Delft, The Netherlands.
authors.forename: Kristina
authors.initials: K
authors.lastname: Djanashvili
mesh_terms: D019793:Fluorescein / Q000737:chemistry* / Q000493:pharmacokinetics; D006367:HeLa Cells; D006695:Holmium / Q000737:chemistry* / Q000493:pharmacokinetics; D006801:Humans; D053758:Nanoparticles / Q000737:chemistry*; D009502:Neutrons; D010087:Oxides / Q000737:chemistry* / Q000493:pharmacokinetics; D010455:Peptides / Q000737:chemistry* / Q000493:pharmacokinetics; D011092:Polyethylene Glycols / Q000737:chemistry* / Q000493:pharmacokinetics; D011868:Radioisotopes / Q000737:chemistry / Q000493:pharmacokinetics; D000068936:Theranostic Nanomedicine
chemical_list: D010087:Oxides; D010455:Peptides; D011868:Radioisotopes; C015462:polyarginine; D011092:Polyethylene Glycols; D019793:Fluorescein; D006695:Holmium