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(Th-227)PO4 core (C) and core +2 shells (C2S) nanoparticles (NPs) as a delivery platform of Th-227 to minimize systemic distribution of decay daughters, Ra-223 and Pb-211. In vitro retention of decay daughters within La(Th-227)PO4 C NPs was influenced by the concentration of reagents used during synthesis, in which the leakage of Ra-223 was between 0.4 +/- 0.2% and 20.3 +/- 1.1% in deionized water. Deposition of two nonradioactive LaPO4 shells onto La(Th-227)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 mu g 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 mu g mL(-1). La(Th-227)PO4 C2S NPs exhibit a high encapsulation and in vitro retention of radionuclides with limited contribution to cellular cytotoxicity for TAT applications.