Synthesis, functionalization and biochemical characterization of ¹⁵³Sm₂O₃-iPSMA-BN NPs as a theranostic nano system for hepatocellular cancer

Hepatocellular carcinoma (HCC) presents limited treatment alternatives due to the few symptoms that the disease exhibits in early stages when surgical interventions are possible. HCC is ranked second as a cause of mortality worldwide due to the limited availability of donors and the high sensibility of healthy hepatic tissue in response to current treatments (mortality rate of 95%). There are pharmacological systems based on specific recognition molecular targets that seek to reduce damage to healthy tissues. These systems are made up of compounds that interact specifically with proteins that are over-expressed in tumor cells. For example, the protein-specific membrane antigen inhibitor (iPSMA) peptide, which interacts with the PSMA protein over expressed mainly in prostate cancer, but also in other tumors including HCC. Another example is the peptide bombesin (BN), which interact with the GRPr protein that is also over-expressed in cells of different types of cancer including the HCC. In this project, the synthesis of samarium oxide nanoparticles (^natSm₂O₃ NPs) was carried out through the precipitation/calcination methodology, Sm₂O₃ NPs presented quasi-spherical shape with hydrodynamic sizes of 83 nm for calcined at 600 ° C and of 149.6 nm for calcined at 900 ° C; both systems showed stability in an aqueous solution with a Z potential greater than -20 mV. ^natSm₂O₃ NPs were activated by neutron irradiation and functionalized with the iPSMA-BN heterodimer to obtain the ¹⁵³Sm₂O₃-iPSMA-BN NPs system, which was evaluated in the HepG2 (PSMA +, RGPr +) and PC3 (PSMA-, RGPr +) cell lines. The nano system showed high internalization, toxicity and affinity for HepG2 cells. Due to the radio luminescent properties observed in the ¹⁵³Sm₂O₃-iPSMA-BN nanoparticles, it was possible to obtain optical images of their biodistribution in BALB-C mice, which showed a main accumulation of the nano system in the liver. These results support the possible use of ¹⁵³Sm₂O₃-iPSMA-BN nanoparticles as a new radiopharmaceutical system in targeted therapy and molecular imaging of HCC. (author)