Introduction: Chrysin (CHY) is a naturally occurring flavonoid known for its anti-inflammatory and antioxidant properties. This systematic review aims to evaluate the photosensitizing and radiosensitizing effects of CHY and its nanoparticle (NP) formulations, and their potential to enhance therapeutic efficacy while reducing treatment-related adverse effects. Methods: This systematic review included 14 in vivo and in vitro studies published before October 21, 2025, that met specific inclusion and exclusion criteria. After screening, 14 studies met the inclusion criteria. Then information from each study was extracted and recorded. Subsequently, a risk-of-bias assessment was conducted for experimental studies, followed by a final analysis of the results. Results: CHY and its NPs, when combined with radiotherapy (RT) and phototherapy (PT), generate singlet oxygen (¹O₂) and various reactive oxygen species (ROS), causing photooxidative damage, DNA injury, cell-cycle arrest often at the G1 phase, and apoptotic cell death. Beyond direct cytotoxicity, CHY participates in key regulatory signaling pathways, including the modulation of apoptotic pathways, thereby enhancing apoptotic responses while increasing the production of inflammatory mediators. Under RT conditions, CHY and its nanoformulations boost γ-irradiation-induced tumor suppression by shifting the redox balance toward oxidative stress, increasing caspase-3 activity, and downregulating survival markers. Conversely, CHY shows notable protective effects in normal cells by reducing oxidative stress, neuroinflammation, and DNA damage through restoring antioxidant defenses, lowering lipid peroxidation, and maintaining neuronal integrity. Conclusion: Overall, CHY and its NPs suggest potential dual roles based on preclinical evidence as photo- and radiosensitizers while also providing protective effects against therapy-induced adverse outcomes.
Marghmaleki et al. (Wed,) studied this question.