DNAzyme hydrogels specifically inhibit the NLRP3 pathway to prevent radiation-induced skin injury in mice
Daijun Zhou, Zhihui Li, Bao Li, Xiang Zhao, Jie Hao, Chuan Xu, Feifan Sun, Dan He, Chaoyang Jiang, Tian Zeng, Dong Li
Abstract
Radiation-induced skin injury (RISI) is a frequent complication of radiotherapy, yet current preventive strategies exhibit suboptimal efficacy. Our previous publications have consistently demonstrated the effectiveness of biomaterials and hydrogels in preventing RISI. Based on comprehensive literature reviews, we speculate that NLRP3 overexpression plays a central role in the development of RISI. Therefore, designing DNAzyme (DZ)-hydrogels with targeted inhibition of NLRP3 overexpression is crucial for preventing RISI.To achieve this, we designed and screened the optimal NLRP3-DZ using bioinformatics, molecular dynamics, and gel electrophoresis methods. We encapsulated the NLRP3-DZ within ZIF-8 to enhance its stability, controlled release, and safety. To enhance the material's transdermal penetration and practicality, we attached the TAT transmembrane peptide. The final preparation and characterization of NLRP3-DZ@ZIF-8/TAT was achieved.In vitro cell models revealed that DZ-hydrogels exhibit high biosafety, effectively inhibit NLRP3 expression, promote cell migration, inhibit cell apoptosis, and possess antibacterial properties. Genomics analysis suggested that DZ-hydrogels may exert these functions by regulating changes in relevant mRNA pathways.Furthermore, we established a mouse model of RISI and found that the material can promote wound healing by regulating proteins associated with apoptosis, oxidative stress, and the inflammatory response. These research findings provide valuable insights for the prevention of RISI using DZ-hydrogels.