Radiosensitization Effect of AGuIX, a Gadolinium-Based Nanoparticle, in Nonsmall Cell Lung Cancer

ACS Appl Mater Interfaces. 2020 Dec 23;12(51):56874-56885. doi: 10.1021/acsami.0c16548. Epub 2020 Dec 16.

Abstract

Radiotherapy is the main treatment for cancer patients. A major concern in radiotherapy is the radiation resistance of some tumors, such as human nonsmall cell lung cancer. However, the radiation dose delivered to the tumors is often limited by the possibility of collateral damage to surrounding healthy tissues. A new and efficient gadolinium-based nanoparticle, AGuIX, has recently been developed for magnetic resonance imaging-guided radiotherapy and has been proven to act as an efficient radiosensitizer. The amplified radiation effects of AGuIX nanoparticles appear to be due to the emission of low-energy photoelectrons and Auger electron interactions. We demonstrated that AGuIX nanoparticles exacerbated radiation-induced DNA double-strand break damage and reduced DNA repair in the H1299 nonsmall cell lung cancer cell line. Furthermore, we observed a significant improvement in tumor cell damage and growth suppression, under radiation therapy, with the AGuIX nanoparticles in a H1299 mouse xenograft model. This study paves the way for research into the radiosensitization mechanism of AGuIX nanoparticles and provides a scientific basis for the use of AGuIX nanoparticles as radiosensitizing drugs.

Keywords: AGuIX nanoparticles; DNA damage repair; NSCLC cell lines; irradiation; radiosensitization effect.

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / radiation effects
  • Antineoplastic Agents / therapeutic use*
  • Apoptosis / drug effects
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Line, Tumor
  • DNA Breaks, Double-Stranded / drug effects
  • DNA Repair / drug effects
  • Gadolinium / chemistry
  • Gadolinium / radiation effects
  • Humans
  • Lung / pathology
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / pathology
  • Male
  • Metal Nanoparticles / chemistry
  • Metal Nanoparticles / radiation effects
  • Metal Nanoparticles / therapeutic use*
  • Mice, Nude
  • Radiation, Ionizing
  • Radiation-Sensitizing Agents / chemistry
  • Radiation-Sensitizing Agents / radiation effects
  • Radiation-Sensitizing Agents / therapeutic use*
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents
  • Radiation-Sensitizing Agents
  • Gadolinium