4.7 Article

Astatine-211-Labeled Gold Nanoparticles for Targeted Alpha-Particle Therapy via Intravenous Injection

Journal

PHARMACEUTICS
Volume 14, Issue 12, Pages -

Publisher

MDPI
DOI: 10.3390/pharmaceutics14122705

Keywords

astatine-211; gold nanoparticles; targeted alpha-particle therapy; cancer therapy; pancreatic cancer; intravenous administration

Funding

  1. JSPS KAKENHI [JP20H05675, JP20H00404, 22J10766]
  2. QiSS program of the OPERA grant [JPMJOP1721]
  3. Uehara Memorial Foundation
  4. JSPS [JP16H06278]

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This study demonstrates the significant anti-tumor effect of 5 nm At-211-AuNPs@mPEG in inhibiting tumor growth in a pancreatic cancer model. AuNPs serve as satisfactory carriers for At-211 delivery, offering a simple and efficient synthesis process and high stability.
Alpha-particle radiotherapy has gained considerable attention owing to its potent anti-cancer effect. At-211, with a relatively short half-life of 7.2 h, emits an alpha particle within a few cell diameters with high kinetic energy, which damages cancer cells with high biological effectiveness. In this study, we investigated the intravenous injection of At-211-labeled gold nanoparticles (AuNPs) for targeted alpha-particle therapy (TAT). Different kinds of surface-modified gold nanoparticles can be labeled with At-211 in high radiochemical yield in 5 min, and no purification is necessary. The in vivo biodistribution results showed the accumulation of 5 nm At-211-AuNPs@mPEG at 2.25% injection dose per gram (% ID/g) in tumors within 3 h via the enhanced permeability and retention (EPR) effect. Additionally, we observed a long retention time in tumor tissues within 24 h. This is the first study to demonstrate the anti-tumor efficacy of 5 nm At-211-AuNPs@mPEG that can significantly suppress tumor growth in a pancreatic cancer model via intravenous administration. AuNPs are satisfactory carriers for At-211 delivery, due to simple and efficient synthesis processes and high stability. The intravenous administration of 5 nm At-211-AuNPs@mPEG has a significant anti-tumor effect. This study provides a new framework for designing nanoparticles suitable for targeted alpha-particle therapy via intravenous injection.

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