Targeted Gold Nanoparticles (AuNPs) for Potent Alpha-Particle Radiotherapy
Abstract
Glioblastoma (GBM) is the most common and aggressive brain cancer. Even with the highest first-year cost (> $120,000) under standard-of-care treatments, the prognosis for GBM patients is dismal. Therefore, it is of great clinical significance to develop novel therapeutic approaches to improve GBM treatment efficacy. Alpha particle radiation therapy with high linear energy transfer (80 keV/micrometer) has a potent therapeutic effect independent of dose rate, cell cycle, and oxygen concentration. A single alpha-particle track can result in lethal DNA double-strand breaks. Astatine-211 (211At) is an attractive alpha emitter for alpha particle radiation therapy because it has the advantages of an optimal half-life (7.2 h) and no long-lived decay "daughter" radionuclides thus avoiding toxicity from daughter radionuclide redistribution. However, traditional 211At radiolabeling methods focusing on At-C chemical bonds have the challenges of having a complicated radio labeling process and low conjugation efficiency. In this study, we develop targeted gold nanoparticles as a novel 211At delivery nanoplatform for alpha particle radiation therapy. In the past year, we have synthesized gold nanoparticles with different sizes and tested their radiolabeling performance. Experimental results demonstrated that the synthesized AuNPs could achieve high radiolabeling efficiency by simply mixing 211At radioisotopes and AuNPs in an aqueous solution at room temperature for a short time. Quantum chemistry calculations have been performed to investigate the bonding mechanism of the At-Au chemical bond. A sigma chemical bond was identified and the valence state for At and Au was determined to be -1 and +1, respectively. Targeting ligands, c(RGDfK) and angiopep-2 were conjugated to the AuNPs for brain cancer targeting.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2020
- Accession Number
- AD1118321
Entities
People
- Yang Liu
Organizations
- Duke University