Preparation and Dosimetry Assessment of 166Dy2O3/166Ho2O3-iPSMA Nanoparticles for Targeted Hepatocarcinoma Radiotherapy.

ABSTRACT

This research aimed to prepare 166Dy2O3-iPSMA/166Ho2O3-iPSMA nanoparticles (166Dy2O3/166Ho2O3-iPSMA NPs) and assess the radiation absorbed dose produced by the nanosystem to hepatic cancer cells by using experimental in vitro and in vivo biokinetic data. Dy2O3NPs were synthesized and functionalized with the prostate-specific membrane antigen inhibitor peptide (iPSMA). Fourier transform infrared (FTIR) spectroscopy, transmission electron microscope (TEM), dynamic light scattering (DSL) and zeta potential analyses indicated the formation of Dy2O3-iPSMA NPs (46.11 ± 13.24 nm). After neutron activation, a stable 166Dy2O3/166Ho2O3- iPSMA nanosystem was obtained, which showed adequate affinity to the PSMA receptor in HepG2 cancer cells (Kd = 9.87 ± 2.27 nM). in vitro studies indicated high 166Dy2O3/166Ho2O3-iPSMA internalization in cancer cells, with high radiation doses to cell nuclei (107 Gy) and cytotoxic effects, resulting in a significant reduction in HepG2 cell viability (decreasing to 2.12 ± 0.31%). After intratumoral administration in mice, the nanosystem biokinetic profile indicated significant retention into the tumoral mass, producing ablative radiation doses (>70 Gy).