A gold nanoparticle system for the enhancement of radiotherapy and simultaneous monitoring of reactive-oxygen-species formation

Abstract

Gold nanoparticles (AuNPs) are known to sensitize cancer cells to radiation therapy (RT) by increasing the deposition of ionizing energy in their immediate vicinity. However, this process of dose enhancement is challenging to monitor because it is heterogeneous at the sub-cellular scale. Furthermore, radiation damage is primarily mediated by reactive oxygen species (ROS) that are produced following water radiolysis. Here, radiation-responsive PEGylated gold nanoparticles (RPAuNPs) were synthesized for the enhanced generation and concurrent detection of ROS in cancer cells and tumors. PEGylated gold particles (20 nm diameter) were functionalized with dihydrorhodamine 123 (DHR-123), a known ROS sensor, to monitor ROS generation in their immediate vicinity. These NPs were able to effectively radiosensitize cells, as measured by increased cell apoptosis following RT. Furthermore, the fluorescence of these RPAuNPs was 7-fold higher after 6 Gy RT due to the local production of ROS near the surface of the NP. Finally, multispectral fluorescence imaging was used to monitor NP-induced ROS in vivo, following conformal RT, in a xenograft model of breast cancer. This theranostic NP system provides a novel approach for monitoring the nanoscale enhancement of RT by high-Z metal NPs.