Targeted Radiosensitizers for MR-Guided Radiation Therapy of Prostate Cancer

Dong Luo, Andrew Johnson, Xinning Wang, Hao Li, Bernadette O. Erokwu, Sarah Springer, Jason Lou, Gopalakrishnan Ramamurthy, Chris A. Flask, Clemens Burda, Thomas J. Meade, James P. Basilion

Research output: Contribution to journalArticlepeer-review

Abstract

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 r1 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.

Original languageEnglish (US)
Pages (from-to)7159-7167
Number of pages9
JournalNano letters
Volume20
Issue number10
DOIs
StatePublished - Oct 14 2020

Keywords

  • MR-guided radiotherapy
  • PSMA targeting
  • Radiosensitizer
  • nanoparticles
  • prostate cancer

ASJC Scopus subject areas

  • Bioengineering
  • Chemistry(all)
  • Materials Science(all)
  • Condensed Matter Physics
  • Mechanical Engineering

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