Gold Coated Lanthanide Phosphate Nanoparticles for Targeted Alpha Generator Radiotherapy

Targeted radiotherapies maximize cytotoxicty to cancer cells. In vivo a-generator targeted radiotherapies can deliver multiple alpha particles to a receptor site dramatically amplifying the radiation dose delivered to the target. The major challenge with alpha-generator radiotherapies is that traditional chelating moieties are unable to sequester the radioactive daughters in the bioconjugate which is critical to minimize toxicity to healthy, non-target tissue. The recoil energy of the Ac-225 daughters following alpha decay will sever any metal-ligand bond used to form the bioconjugate. This work demonstrates that an engineered multilayered nanoparticle-antibody conjugate can deliver multiple alpha radiations and contain the decay daughters of Ac-225 while targeting biologically relevant receptors in a female BALB/c mouse model. These multi-shell nanoparticles combine the radiation resistance of lanthanide phosphate to contain Ac-225 and its radioactive decay daughters, the magnetic properties of gadolinium phosphate for easy separation, and established gold chemistry for attachment of targeting moieties.