Synthesis, chemical and biochemical characterization of Lu₂O₃-iPSMA nanoparticles activated by neutron irradiation

Among the nanomaterials, rare sesquioxides (lanthanide oxides such as Lu₂O₃) are of interest due to their adequate thermal conductivity, excellent chemical stability, and high light output. The prostate-specific membrane antigen (PSMA) is an integral multifunctional protein overexpressed in various types of cancer cells. The radiolabeled PSMA inhibitor peptides (iPSMA) have demonstrated their usefulness as specific probes in the treatment and detection of a wide variety of neoplasms, mainly due to their high in vivo recognition by the PSMA protein. The objective of this research was to synthesize Lu₂O₃-iPSMA nanoparticles (NPs) and characterize their physicochemical properties before and after neutron activation, as well as to assess their biodistribution profile and in vitro potential to target cells overexpressing PSMA. The Lu₂O₃ NPs were synthesized by the precipitation-calcination method and conjugated to the iPSMA peptide using DOTA (1,4,7,10-tetraazocyclodecane-N,N',N″,N‴-tetraacetic acid) as a linking agent. Results of the physicochemical characterization by FT-IR and UV-Vis spectroscopies, SEM, TEM, DLS, HRTEM, SAED, DSC-TGA, and X-ray diffraction indicated the formation of Lu₂O₃-iPSMA NPs (diameter of 29.98 ± 9.07 nm), which were not affected in their physicochemical properties after neutron activation. ¹⁷⁷Lu₂O₃-iPSMA NPs showed high affinity (K_d = 5.7 ± 1.9 nM) for the PSMA protein, evaluated by the saturation assay on HepG2 hepatocellular carcinoma cells (PSMA-positive). The biodistribution profile of the nanosystem in healthy mice showed the main uptake in the liver. After irradiation, radioactive Lu₂O₃-iPSMA NPs exhibited radioluminescent properties, making the in vivo acquisition of their biodistribution, via optical imaging, possible. The results obtained from this research validate the execution of additional preclinical studies with the objective of evaluating the potential of the ¹⁷⁷Lu₂O₃-iPSMA NPs for the targeted radiotherapy and in vivo imaging of tumors overexpressing the PSMA protein.