Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 9744-9755 |
| Number of pages | 12 |
| Journal | Nanoscale |
| Volume | 12 |
| Issue number | 17 |
| DOIs | |
| State | Published - May 7 2020 |
Funding
This research was supported by an appointment to the Oak Ridge National Laboratory Nuclear Engineering Science Laboratory Synthesis program, sponsored by the US Department of Energy and administered by the Oak Ridge Institute for Science and Education; Virginia Commonwealth University with the support of the Mechanical and Nuclear Engineering Department and the NRC-HQ-84-14-FOA-002, Faculty Development Program in Radiation Detection and Health Physics at Virginia Commonwealth University; the US Department of Energy Isotope Program, managed by the Office of Science for Nuclear Physics; and ORNL Laboratory Directed Research and Development. The authors would like to thank the staff of the Nuclear and Radiochemistry Group at Oak Ridge National Laboratory for their isotope production and purification contributions.
| Funders | Funder number |
|---|---|
| Mechanical and Nuclear Engineering Department | NRC-HQ-84-14-FOA-002 |
| Office of Science for Nuclear Physics | |
| US Department of Energy | |
| Oak Ridge Institute for Science and Education | |
| Laboratory Directed Research and Development | |
| Virginia Commonwealth University |
