Quantitative encapsulation and retention of 227Th and decay daughters in core-shell lanthanum phosphate nanoparticles.

Targeted alpha therapy (TAT) offers great promise for treating recalcitrant tumors and micrometastatic cancers. One drawback of TAT is the potential damage to normal tissues and organs due to the relocation of decay daughters from the treatment site. The present study evaluates La(227Th)PO4 core (C) and core +2 shells (C2S) nanoparticles (NPs) as a delivery platform of 227Th to minimize systemic distribution of decay daughters, 223Ra and 211Pb. In vitro retention of decay daughters within La(227Th)PO4 C NPs was influenced by the concentration of reagents used during synthesis, in which the leakage of 223Ra was between 0.4 ± 0.2% and 20.3 ± 1.1% in deionized water. Deposition of two nonradioactive LaPO4 shells onto La(227Th)PO4 C NPs increased the retention of decay daughters to >99.75%. The toxicity of the nonradioactive LaPO4 C and C2S NP delivery platforms was examined in a mammalian breast cancer cell line, BT-474. No significant decrease in cell viability was observed for a monolayer of BT-474 cells for NP concentrations below 233.9 µg mL-1, however cell viability decreased below 60% when BT-474 spheroids were incubated with either LaPO4 C or C2S NPs at concentrations exceeding 29.2 µg mL-1. La(227Th)PO4 C2S NPs exhibit a high encapsulation and in vitro retention of radionuclides with limited contribution to cellular cytotoxicity for TAT applications.

Multifunctional GdVO4:Eu core-shell nanoparticles containing 225Ac for targeted alpha therapy and molecular imaging.

Gadolinium vanadate nanoparticles (NPs) doped with europium, in concentrations between 5-40%, were synthesized via an aqueous route to prove their multimodal imaging functionalities and their performance as radionuclide carriers for targeted alpha therapy. Core-shell Gd0.8Eu0.2VO4 NPs were doped with the α-emitting actinium-225 to assess the in vitro retention of 225Ac and its decay daughters; francium-221 and bismuth-213. Gd0.8Eu0.2VO4 core-shell NPs were obtained using a precipitation synthesis route having a tetragonal system, a spherical morphology, and a uniform particle size distribution. Gd0.8Eu0.2VO4 core-shell NPs displayed the characteristic intense emission at 618 nm (red) and paramagnetic behavior of Eu and Gd cations, respectively. Partial retention of radionuclides was obtained with Gd0.8Eu0.2VO4 core NPs, while deposition of two nonradioactive Gd0.8Eu0.2VO4 shells significantly decreased the leakage of both 225Ac and 221Fr. The luminescence and magnetic functionalities as well as radionuclide retention capabilities of Gd0.8Eu0.2VO4 core-shell NPs demonstrate their potential for biomedical applications.