Targeted Gold Nanoparticles (AuNPs) for Potent Alpha-Particle Radiotherapy Brain Cancer
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/micrometers) 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 radiolabeling 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 demonstrated that the developed gold nanoparticles can selectively accumulate in the brain tumor but not surrounding healthy brain tissue. We also performed preliminary in vivo toxicity study and therapeutic efficacy test. Preliminary experiment results demonstrated that alpha emitter radiation therapy with 211At-loaded gold nanoparticles can substantially reduce tumor growth after intratumoral administration using murine animal models.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2021
- Accession Number
- AD1155386
Entities
People
- Yang Liu
Organizations
- Duke University