期刊
PLOS ONE
卷 8, 期 1, 页码 -出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0054531
关键词
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资金
- Isotope Production/Distribution Program
- Office of Nuclear Physics of the U. S. Department of Energy (DOE)
- DOE Nuclear Energy University Program Graduate Fellowship
- University of Tennessee
- Graduate School of Medicine
- Center for Nanophase Materials Sciences, which is sponsored at Oak Ridge National Laboratory by the Office of Basic Energy Sciences, U.S. Department of Energy
- ORNL is managed by UT-Battelle, LLC, for the U.S. Department of energy [DE-AC05-00OR22725]
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.
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