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 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.
Department of Chemistry and University of Missouri Research Reactor, University of Missouri, Columbia, Missouri, USA.
Mark F
MF
McLaughlin
Jonathan
J
Woodward
Rose A
RA
Boll
Jonathan S
JS
Wall
Adam J
AJ
Rondinone
Stephen J
SJ
Kennel
Saed
S
Mirzadeh
J David
JD
Robertson
D000512:Alpha Particles; D000818:Animals; D000906:Antibodies / Q000008:administration & dosage; D002614:Chelating Agents / Q000737:chemistry; D005260:Female; D006046:Gold / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D018796:Immunoconjugates / Q000008:administration & dosage; D007811:Lanthanum / Q000737:chemistry* / Q000494:pharmacology; D053768:Metal Nanoparticles / Q000008:administration & dosage / Q000737:chemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D010710:Phosphates / Q000737:chemistry* / Q000494:pharmacology; D011878:Radiotherapy; D014018:Tissue Distribution
D000906:Antibodies; D002614:Chelating Agents; D018796:Immunoconjugates; D010710:Phosphates; C551148:lanthanide phosphate; D007811:Lanthanum; D006046:Gold