Physicochemical Tools: Toward a Detailed Understanding of the Architecture of Targeted Radiotherapy Nanoparticles

Abstract

Targeted radiotherapy is proving to be an effective alternative to external beam radiotherapy for cancer treatment. Gold nanoparticles are bio-compatible, commercially available and readily functionalised, which makes them perfect candidates for the delivery of cytotoxic radionuclides labelled with antibodies to proteins abnormally expressed on cancer tissue. However, there is a lack of information regarding the efficacy of the successive modification steps involved in the functionalisation process, as well as of the actual final state of the nanoparticles prior to preclinical tests, which results in a very inefficient screening and that will further impact on biological barriers, such as half-life interactions with serum proteins. Here, gold nanoparticles (15 nm diameter) were functionalised with linkers for antibody and radionuclide conjugation, following a well-stablished method. Successful coating of the gold nanoparticles was demonstrated using state-of-the-art physico-chemical techniques, which include TEM, AF4-UV-ICPMS-MALS, Raman spectroscopy and force-distance spectroscopy, which have led to an accurate description of the hydrodynamic diameter of the functionalized NPs and also about the adhesion energy and elastic properties of the modified NPs. Successive steps involved in the coating led to an organic shell of 12 nm diameter and no nanoparticle aggregation was observed. This may be a consequence of a decrease (or even the total absence) of water adsorption on the metal surface and/or of the organic labelling, that decreases the surface tension of the particles as estimated from the atomic force microscopy force-distance curves. Radiolabelling of gold nanoparticles pre-screened using these physico-chemical tools with 177 Lu resulted in > 75% efficiency.

Cu@Au self-assembled nanoparticles as SERS-active substrates for (bio)molecular sensing

“…2A) and Au NPs (Fig. 2B), which were stabilized with a PEG-SH shell to prevent aggregation (5.6 ± 0.3 nm thick) [39]. According to Eq.…”

“…1, the UV/vis detector allowed for NPs hydrodynamic size quantification based on the strong dependence of UV absorption of plasmonic particles with size [40][41][42]. The same calibration curve of Au standards reported elsewhere was used for the calculation of retention time [39]. Further, online coupling of the asymmetric flow field flow fractionation (AF4) coupled UV/vis system and ICPMS provided additional, specific multielement detection and the capability to distinguish metal NPs from artefacts [43].…”