UV emitting nanoparticles enhance the effect of ionizing radiation in 3D lung cancer spheroids. (2nd September 2022)

• Record Type: Journal Article
• Authors: Tran, Thao Anh; Kappelhoff, Jan; Jüstel, Thomas; Anderson, R. Rox; Purschke, Martin
• Is Part Of: International journal of radiation biology. Volume 98:Number 9(2022)
• Page Start: 1484
• Page End: 1494
• Publication Date: 2022-09-02
• Subjects: 3D cancer spheroids -- UVC emitting nanoparticles -- X-irradiation -- hypoxia -- apoptosis -- cell cycle arrest -- nanoparticle uptake; Radiation -- Physiological effect -- Periodicals; Radiobiology -- Periodicals; 571.45
• DOI: 10.1080/09553002.2022.2027541
• Languages: English
• ISSNs: 0955-3002

Abstract

Abstract: Purpose: Radiation therapy for cancer is limited by damage to surrounding normal tissues, and failure to completely eradicate a tumor. This study investigated a novel radiosensitizer, composed of lutetium phosphate nanoparticles doped with 1% praseodymium and 1.5% neodymium cations (LuPO4 :Pr 3+, Nd 3+ ). During X-ray exposure, the particles emit UVC photons (200–280 nm), resulting in increased tumor cell death, by oxygen-independent UVC-induced damage. Methods and Materials: Specially designed LuPO4 :Pr 3+, Nd 3+ nanoscintillator particles were characterized by dynamic light scattering, TEM and emission spectroscopy upon excitation. Cell death was determined by reduction in tumor spheroid growth over a 3-week period using a 3 D A549 lung cancer model. Cell cycle was evaluated by flow cytometry and cell death pathways were assessed by Annexin V/PI stain as well as quantify apoptotic bodies. Results: Lung cancer cells expressed no long-term or nonspecific toxicity when incubated with LuPO4 :Pr 3+, Nd 3+ nanoscintillators. In contrast, there was significant growth inhibition of cell spheres treated with 2.5 mg/ml LuPO4 :Pr 3+, Nd 3+ in combination with ionizing radiation (4 or 8 Gy X-ray), compared to radiation alone. Homogeneous distribution of small NPs throughout the entire sphere resulted in more pronounced lethality and growth inhibition, compared to particle distribution limited to the outer cell layers. Growth inhibition after the combined treatment was caused by necrosis, apoptosis and G2 /M cell cycle arrest. Conclusions: Newly designed UVC-emitting nanoscintillators (LuPO4 :Pr 3+, Nd 3+ ) in combination with ionizing radiation cause tumorsphere growth inhibition by inducing cell cycle arrest, apoptosis and necrosis. UVC-emitting nanoparticles offer a promising new strategy for enhancing local tumor response to ionizing radiation treatment. Graphical abstract text: UF0001 Our group has developed a new nanosized UVC emitting radiosensitizer to significantly enhance the biological effect of ionizing radiation. The nanoparticles absorb X-rays and convert them into lower energetic UVC photons (200–280 nm) which results in DNA damage, cell cycle arrest, and ultimately cell death. The combined treatment caused a significant size decrease of 3 D lung cancer spheroids.