Nanozeolite bioconjugates labeled with ²²³Ra for targeted alpha therapy

Area of Science:

• Nuclear Medicine
• Nanotechnology
• Oncology

Background:

• Alpha particle emitting isotopes like radium-223 (223Ra) are promising for radionuclide therapy due to high cytotoxicity.
• A key challenge for 223Ra targeted therapy is the lack of suitable bifunctional ligands.
• Nanozeolite-Substance P bioconjugates were investigated as novel delivery vehicles for 223Ra.

Purpose of the Study:

• To develop and evaluate nanozeolite-Substance P bioconjugates for targeted alpha therapy using 223Ra.
• To assess the stability, receptor affinity, and cytotoxicity of 223Ra-labeled bioconjugates.

Main Methods:

• Synthesis of A-type nanozeolite (NaA) and conjugation with Substance P (5-11) peptide.
• Labeling of nanozeolite bioconjugates with 223Ra via cation exchange.
• Characterization of bioconjugates and evaluation of their in vitro stability, NK-1 receptor affinity, and cytotoxicity against glioma cells.

Main Results:

• The 223Ra-labeled nanozeolite bioconjugate demonstrated high in vitro retention of 223Ra (>99%) and its decay products (90-95%) for 6 days.
• The construct exhibited significant receptor affinity for NK-1 receptor-expressing glioma cells.
• A potent cytotoxic effect against glioma cells was observed in vitro.

Conclusions:

• Substance P-functionalized nanozeolite-A provides a viable strategy for utilizing 223Ra as an in vivo generator for targeted glioma therapy.
• This approach offers a promising solution for overcoming previous limitations in radium-based targeted radionuclide therapy.