Fate of organic functionalities conjugated to theranostic nanoparticles upon their activation

Abstract

Neutron activation is widely applied for thepreparation of radioactive isotopes to be used in imaging and/or therapy. The type of diagnostic/therapeutic agents varies fromsmall chelates coordinating radioactive metal ions to complexnanoparticulate systems. Design of these agents often relies onconjugation of certain organic functionalities that determine theirpharmacokinetics, biodistribution, targeting, and cell-penetratingabilities, or simply on tagging them with an optical label. Theconjugation chemistry at the surface of nanoparticles and theirfinal purification often require laborious procedures that becomeeven more troublesome when radioactive materials are involved.This study represents a thorough investigation on the effects ofneutron activation on the organic moieties of functionalizednanoparticles, with special focus on166Ho2O3particles conjugated with PEG-fluorescein and PEG-polyarginine motives.Spectroscopic and thermogravimetric analyses demonstrate only a limited degradation of PEG-fluorescein upon irradiation of theparticles up to 10 h using a thermal neutronflux of 5×1016m−2s−1. Cell experiments show that the polyarginine-basedmechanisms of membrane penetration remain unaltered after exposure of the functionalized particles to the mixedfield ofneutrons and gammas present during activation. This confirms that radiation damage on the PEG-polyarginines is minimal.Intrinsic radiations from166Ho do not seem to affect the integrity of conjugated organic material. Thesefindings open up a newperspective to simplify the procedures for the preparation of functionalized metal-based nanosystems that need to be activated byneutron irradiation in order to be applied for diagnostic and/or therapeutic purposes.