Gold coated lanthanide phosphate nanoparticles for targeted alpha generator radiotherapy.

Targeted radiotherapies maximize cytotoxicty to cancer cells. In vivo α-generator targeted radiotherapies can deliver multiple α particles to a receptor site dramatically amplifying the radiation dose delivered to the target. The major challenge with α-generator radiotherapies is that traditional ch...

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Main Authors: Mark F McLaughlin, Jonathan Woodward, Rose A Boll, Jonathan S Wall, Adam J Rondinone, Stephen J Kennel, Saed Mirzadeh, J David Robertson
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2013-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3548790?pdf=render
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author Mark F McLaughlin
Jonathan Woodward
Rose A Boll
Jonathan S Wall
Adam J Rondinone
Stephen J Kennel
Saed Mirzadeh
J David Robertson
author_facet Mark F McLaughlin
Jonathan Woodward
Rose A Boll
Jonathan S Wall
Adam J Rondinone
Stephen J Kennel
Saed Mirzadeh
J David Robertson
author_sort Mark F McLaughlin
collection DOAJ
description Targeted radiotherapies maximize cytotoxicty to cancer cells. In vivo α-generator targeted radiotherapies can deliver multiple α particles to a receptor site dramatically amplifying the radiation dose delivered to the target. The major challenge with α-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 (225)Ac daughters following α 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 α radiations and contain the decay daughters of (225)Ac 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 (225)Ac 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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spelling doaj.art-1a3a1583aa87460787fc214aaf7959c62022-12-22T00:47:20ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0181e5453110.1371/journal.pone.0054531Gold coated lanthanide phosphate nanoparticles for targeted alpha generator radiotherapy.Mark F McLaughlinJonathan WoodwardRose A BollJonathan S WallAdam J RondinoneStephen J KennelSaed MirzadehJ David RobertsonTargeted radiotherapies maximize cytotoxicty to cancer cells. In vivo α-generator targeted radiotherapies can deliver multiple α particles to a receptor site dramatically amplifying the radiation dose delivered to the target. The major challenge with α-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 (225)Ac daughters following α 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 α radiations and contain the decay daughters of (225)Ac 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 (225)Ac and its radioactive decay daughters, the magnetic properties of gadolinium phosphate for easy separation, and established gold chemistry for attachment of targeting moieties.http://europepmc.org/articles/PMC3548790?pdf=render
spellingShingle Mark F McLaughlin
Jonathan Woodward
Rose A Boll
Jonathan S Wall
Adam J Rondinone
Stephen J Kennel
Saed Mirzadeh
J David Robertson
Gold coated lanthanide phosphate nanoparticles for targeted alpha generator radiotherapy.
PLoS ONE
title Gold coated lanthanide phosphate nanoparticles for targeted alpha generator radiotherapy.
title_full Gold coated lanthanide phosphate nanoparticles for targeted alpha generator radiotherapy.
title_fullStr Gold coated lanthanide phosphate nanoparticles for targeted alpha generator radiotherapy.
title_full_unstemmed Gold coated lanthanide phosphate nanoparticles for targeted alpha generator radiotherapy.
title_short Gold coated lanthanide phosphate nanoparticles for targeted alpha generator radiotherapy.
title_sort gold coated lanthanide phosphate nanoparticles for targeted alpha generator radiotherapy
url http://europepmc.org/articles/PMC3548790?pdf=render
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