Targeted Radiosensitizers for MR-Guided Radiation Therapy of Prostate Cancer

• Published in: Nano letters 2020-10, Vol.20 (10), p.7159-7167
• Main Authors: Luo, Dong, Johnson, Andrew, Wang, Xinning, Li, Hao, Erokwu, Bernadette O, Springer, Sarah, Lou, Jason, Ramamurthy, Gopalakrishnan, Flask, Chris A, Burda, Clemens, Meade, Thomas J, Basilion, James P
• Format: Article
• Language: English
• Subjects: Cell Line, Tumor; Gold; Humans; Male; Metal Nanoparticles; Prostatic Neoplasms - diagnostic imaging; Prostatic Neoplasms - radiotherapy
• ISSN: 1530-6984; 1530-6992
• DOI: 10.1021/acs.nanolett.0c02487

Adjuvant radiotherapy is frequently prescribed to treat cancer. To minimize radiation-related damage to healthy tissue, it requires high precision in tumor localization and radiation dose delivery. This can be achieved by MR guidance and targeted amplification of radiation dose selectively to tumors by using radiosensitizers. Here, we demonstrate prostate cancer-targeted gold nanoparticles (AuNPs) for MR-guided radiotherapy to improve the targeting precision and efficacy. By conjugating Gd­(III) complexes and prostate-specific membrane antigen (PSMA) targeting ligands to AuNP surfaces, we found enhanced uptake of AuNPs by PSMA-expressing cancer cells with excellent MR contrast and radiation therapy outcome in vitro and in vivo. The AuNPs binding affinity and r 1 relaxivity were dramatically improved and the combination of Au and Gd­(III)­provided better tumor suppression after radiation. The precise tumor localization by MR and selective tumor targeting of the PSMA-1-targeted AuNPs could enable precise radiotherapy, reduction in irradiating dose, and minimization of healthy tissue damage.