Abstract
Targeted radiotherapies maximize cytotoxicty to cancer cells. In vivo α generators such as 225Ac, which emits four α particles in its decay chain, can significantly amplify the radiation dose delivered to the target site. However, renal dose from unbound 213Bi escaping during the decay process limits the dose of 225Ac that can be administered. Traditional chelating moieties are unable to sequester the radioactive daughters because of the high recoil energy from alpha particle emission. To counter this, we demonstrate that an engineered multilayered nanoparticle-antibody conjugate can both deliver α radiation and contain the decay daughters of the in vivo α-generator 225Ac while targeting biologically relevant receptors. These multi-shell nanoparticles combine the radiation resistance of crystalline lanthanide phosphate to encapsulate and contain 225Ac and its radioactive decay daughters, the magnetic properties of gadolinium phosphate for easy separation, and established surface chemistry of gold for attachment of nanoparticles to targeting antibodies.
