Engineering cuttlefish melanin nanoparticles: A dual-action therapy for acute radiation syndrome and combined radiation-wound injuries via regulating Bcl-2 family proteins and caspases in the apoptotic process

Ionizing radiation (IR) injuries are featured as acute radiation syndrome (ARS) and localized combined radiation-wound injury (CRWI). While scavenging reactive oxygen species (ROS) is a key strategy for mitigating IR-induced damage, the development of effective marine natural biomaterials for treatment remains rare and challenging. In this study, we engineered cuttlefish melanin nanoparticles (CMNs) and incorporated them into a poly (vinyl alcohol) (PVA) and sodium alginate (SA) matrix, enabling the in situ synthesis of PVA/SA@CMNs (PS@CMNs) hydrogels with multifaceted therapeutic benefits. CMNs pretreatment significantly alleviated radiation-induced damage in ARS models, particularly by protecting the hematopoietic and immune systems. Furthermore, PS@CMNs hydrogels exhibited exceptional antioxidant, photothermal antibacterial, and biodegradable properties than CMNs. Upon near-infrared laser irradiation, these hydrogels accelerated the healing of bacteria-infected CRWI. The therapeutic mechanism involves the regulation of apoptosis-related proteins, including Bax and Bcl-2, effectively inhibiting the apoptotic process. This study highlights the dual-action potential of CMNs and PS@CMNs hydrogels in mitigating radiation damage and promoting wound healing, offering a promising marine biomaterial-based approach for radiation protection and regenerative medicine.