Gold nanoparticles (AuNPs) have been extensively studied in cancer treatment research since they have special physicochemical characteristics such as facile surface functionalization with various chemical groups, low toxicity, favorable biocompatibility, and the ability to passively accumulate in tumors through the enhanced permeability and retention (EPR) effect. Prostate cancer cells exhibit an overexpression of the Prostate-Specific Membrane Antigen (PSMA), which therefore represents an ideal candidate for the development of nanoplatforms targeting PSMA overexpressed on these cells. Lutetium-177 (177Lu) is a β-particle emitter with a half-life of 6.7 days. This radionuclide is very promising for the development of theranostic platforms as it emits β− particles, which are suitable for therapy, and γ-photons, capable of SPECT imaging. The combination of 177Lu with AuNPs functionalized with PSMA for targeted delivery offers a promising tool for both diagnosis and therapy of prostate cancer. In this study, we focused on the synthesis and in vitro evaluation of PSMA-targeted AuNPs radiolabeled with 177Lu. The AuNPs were functionalized with the TADOTAGA chelator, which enables effective radiolabeling with the radiometal, as well as with a PSMA molecule, which comprises the PSMA targeting moiety (vehicle) of the nanoconstruct. Radiolabeling of the functionalized AuNPs with 177Lu was fast and robust. Subsequent studies focused on the in vitro stability and cellular interaction with two prostate cancer cell lines with different PSMA expression levels, in both 2D and 3D cell cultures, to assess effective targeting. Results indicate that radiolabeled AuNPs exhibit selective interaction with PSMA-expressing cells and present a stronger in vitro cytotoxic effect when functionalized with the PSMA molecule, confirming their potential as theranostic agents and warranting further investigation in LNCaP tumor-bearing mice.
Apostolopoulou et al. (2026) studied this question.