Fluorinated diselenide nanoparticles for radiosensitizing therapy of cancer

• Published in: Free radical biology & medicine Vol. 187; pp. 132 - 140
• Main Authors: Vetrik, Miroslav, Kucka, Jan, Kobera, Libor, Konefal, Rafal, Lobaz, Volodymyr, Pavlova, Ewa, Bajecny, Martin, Heizer, Tomas, Brus, Jiri, Sefc, Ludek, Pratx, Guillem, Hruby, Martin
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.07.2022
• Subjects: Diselenide; Fluorosomes; Hypoxia; Radiosensitizers; Redox systems; Self-assembly nanoparticles; Radiosensitizers; Hypoxia; Redox systems; Diselenide; Self-assembly nanoparticles; Fluorosomes
• ISSN: 0891-5849; 1873-4596
• DOI: 10.1016/j.freeradbiomed.2022.05.015

Radiation resistance of cancer cells represents one of the major challenges in cancer treatment. The novel self-assembled fluoralkylated diselenide nanoparticles (fluorosomes) based on seleno-l-cystine (17FSe2) possess redox-active properties that autocatalytically decompose hydrogen peroxide (H2O2) and oxidize the intracellular glutathione (GSH) that results in regulation of cellular oxidative stress. Alkylfluorinated diselenide nanoparticles showed a significant cytotoxic and radiosensitizing effect on cancer cells. The EL-4 tumor-bearing C56BL/6 mice treated with 17FSe2 followed by fractionated radiation treatment (4 × 2Gy) completely suppressed tumor growth. Our results suggest that described diselenide system behaves as a potent radiosensitizer agent targeting tumor growth and preventing tumor recurrence. Alkylfluorinated diselenium ROS responsive nanoparticles show cytotoxic preference of highly aggressive cancer cells. Compact nanoparticles underwent morphological changes as a response in ROS and GSH environment triggering autocatalytic reactions that lead preferably to the death of cancer cells. In vivo models show radiosensitizing effect together with cancer recurrence prevention after radiation treatment therapy. [Display omitted] Alkylfluorinated diselenium ROS responsive nanoparticles:•Forms compact nanoparticles with a fluorinated core.•Underwent morphological changes in ROS and GSH environment triggering autocatalytic reactions leading preferably to the death of cancer cells.•Show radiosensitive properties by autocatalytic reaction of seleninic acid generated due to presence of H2O2.