Functionalized nanomaterial based on tungsten disulfide WS₂ and gold nanoparticles activated by radiation for cancer therapy

Cancer remains one of the leading causes of mortality worldwide. Traditional therapies like Photodynamic Therapy (PDT) and Radiotherapy have limitations related to low efficacy and side effects. PDT typically relies on UV–NIR light to activate a photosensitizer that generates reactive oxygen species (ROS), but it is restricted to superficial tumors due to limited light penetration. Similarly, Radiotherapy uses high-energy X-rays to directly damage cancer cells, leading as well to numerous side effects on healthy tissues. Recently, the use of X-rays in PDT has emerged as a promising alternative due to deeper tissue penetration. In this context, nanotechnology offers new opportunities, with 2D nanomaterials showing promise as radiosensitizers due to their unique physicochemical properties. This study presents a novel biocompatible nanomaterial designed as a radiosensitizer, consisting of functionalized 2D nanocrystals (WS₂) combined with gold nanoparticles, that can be internalized by cells and activated by low-energy X-rays to locally enhance the radiation effect and selectively kill cancer cells. The novel nanomaterial was synthesized and characterized using TEM, STEM, UV-Vis spectroscopy and DLS. The ability of the nanomaterial to generate ROS under X-ray irradiation was assessed through cell-free experiments using the specific ROS-sensitive probe 1,3-diphenylisobenzofuran. Subsequently, in vitro experiments were conducted on HT-29 cancer cells to evaluate the cytotoxicity and efficacy of the novel nanomaterial at different concentrations and X-ray doses. Cell viability was determined by cell counting, cell cycle analysis was assessed by flow cytometry and DNA damage was evaluated using γ-H2AX antibody followed by confocal microscopy analysis. Oxidative stress within the cells was evaluated through the detection of oxidized nucleobases (8-oxo-7,8-dihydroguanosine) by UHPLC-MS/MS, as well as by analyzing the gene expression levels of oxidative stress-related markers, including SOD-1, SOD-2, and HO-1. Our findings revealed that this nanomaterial amplifies the effect of radiation in cancer cells, acting as an effective radiosensitizer.