Framework nucleic acids as promising reactive oxygen species scavengers for anti-inflammatory therapy.

Reactive oxygen species (ROS) are an array of derivatives of molecular oxygen that participate in multiple physiological processes under the control of redox homeostasis. However, under pathological conditions, the over-production of ROS often leads to oxidative stress and inflammatory reactions, indicating a potential therapeutic target. With the rapid development of nucleic acid nanotechnology, scientists have exploited various DNA nanostructures with remarkable biocompatibility, programmability, and structural stability. Among these novel organic nanomaterials, a group of skeleton-like framework nucleic acid (FNA) nanostructures attracts the most interest due to their outstanding self-assembly, cellular endocytosis, addressability, and functionality. Surprisingly, different FNAs manifest similarly satisfactory antioxidative and anti-inflammatory effects during their biomedical application process. First, they are intrinsically endowed with the ability to neutralize ROS due to their DNA nature. Therefore, they are extensively involved in the complicated inflammatory signaling network. Moreover, the outstanding editability of FNAs also allows for flexible modifications with nucleic acids, aptamers, peptides, antibodies, low-molecular-weight drugs, and so on, thus further strengthening the targeting and therapeutic ability. This review focuses on the ROS-scavenging potential of three representative FNAs, including tetrahedral framework nucleic acids (tFNAs), DNA origami, and DNA hydrogels, to summarize the recent advances in their anti-inflammatory therapy applications. Although FNAs exhibit great potential in treating inflammatory diseases as promising ROS scavengers, massive efforts still need to be made to overcome the emerging challenges in their clinical translation.