Radiation dose enhancement using gold nanoparticles with a diamond linear accelerator target: a multiple cell type analysis

Abstract

Radiotherapy (RT) is an effective cancer treatment modality, but standard RT often causes collateral damage to nearby healthy tissues. To increase therapeutic ratio, radiosensitization via gold nanoparticles (GNPs) has been shown to be effective. One challenge is that megavoltage beams generated by clinical linear accelerators are poor initiators of the photoelectric effect. Previous computer models predicted that a diamond target beam (DTB) will yield 400% more low-energy photons, increasing the probability of interacting with GNPs to enhance the radiation dose by 7.7-fold in the GNP vicinity. After testing DTB radiation coupled with GNPs in multiple cell types, we demonstrate decreased head-and-neck cancer (HNC) cell viability in vitro and enhanced cell-killing in zebrafish xenografts compared to standard RT. HNC cell lines also displayed increased double-stranded DNA breaks with DTB irradiation in the presence of GNPs. This study presents preclinical responses to GNP-enhanced radiotherapy with the novel DTB, providing the first functional data to support the theoretical evidence for radiosensitization via GNPs in this context, and highlighting the potential of this approach to optimize the efficacy of RT in anatomically difficult-to-treat tumors.

Insights into Gold Nanoparticles Possibilities for Diagnosis and Treatment of the Head and Neck Upper Aerodigestive Tract Cancers

“…To achieve any enhancement in radiotherapy (RT), AuNPs must be delivered to and internalized by cancer cells. They enter cells through receptor-mediated endocytosis (RME) [ 39 ]; thus, combining AuNPs with radiotherapy and chemotherapy is promising for a complete treatment modality [ 40 ], promoting tumor cell death mainly due to apoptosis [ 36 ].…”

Biodegradable Ultrasmall-in-Nano Architectures Loaded with Cisplatin Prodrug in Combination with Ionizing Radiation Induces DNA Damage and Apoptosis in Pancreatic Ductal Adenocarcinoma

“…Although a few studies have investigated the effect of gold USNPs in combination with radiation, it remains difficult to compare the results as size, shape, surface charge and coating can influence the effect in biological systems [ 32 , 33 ]. Therefore, we also investigated the effect of our gold USNPs at a diameter of 3 nm with and without radiation.…”

Red, green, and blue radio-luminescent polymer dots doped with heteroleptic tris-cyclometalated iridium complexes

“… 3 Among these medical applications, linear accelerators are used to deliver radiation, including hard X-rays and electron beams, to visualize and induce cell death in targeted areas. 4 The advantages of using X-rays and electron beams include their high biological permeability, which allows non-invasive imaging, high resolution and is already used in many clinical settings. 5 There is substantial interest in using these technologies to develop novel imaging and therapeutic modalities by using photo-functional nanomaterials.…”