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.

A Novel Bioswitchable miRNA Mimic Delivery System: Therapeutic Strategies Upgraded from Tetrahedral Framework Nucleic Acid System for Fibrotic Disease Treatment and Pyroptosis Pathway Inhibition.

There has been considerable interest in gene vectors and their role in regulating cellular activities and treating diseases since the advent of nucleic acid drugs. MicroRNA (miR) therapeutic strategies are research hotspots as they regulate gene expression post-transcriptionally and treat a range of diseases. An original tetrahedral framework nucleic acid (tFNA) analog, a bioswitchable miR inhibitor delivery system (BiRDS) carrying miR inhibitors, is previously established; however, it remains unknown whether BiRDS can be equipped with miR mimics. Taking advantage of the transport capacity of tetrahedral framework nucleic acid (tFNA) and upgrading it further, the treatment outcomes of a traditional tFNA and BiRDS at different concentrations on TGF-ß- and bleomycin-induced fibrosis simultaneously in vitro and in vivo are compared. An upgraded traditional tFNA is designed by successfully synthesizing a novel BiRDS, carrying a miR mimic, miR-27a, for treating skin fibrosis and inhibiting the pyroptosis pathway, which exhibits stability and biocompatibility. BiRDS has three times higher efficiency in delivering miRNAs than the conventional tFNA with sticky ends. Moreover, BiRDS is more potent against fibrosis and pyroptosis-related diseases than tFNAs. These findings indicate that the BiRDS can be applied as a drug delivery system for disease treatment.

Collision of Commonality and Personalization: Better Understanding of the Periosteum.

The periosteum is quite essential for bone repair. The excellent osteogenic properties of periosteal tissue make it a popular choice for accelerated osteogenesis in tissue engineering. With advances in research and technology, renewed attention has been paid to the periosteum. Recent studies have shown that the complexity of the periosteum is not only limited to histological features but also includes genetic and phenotypic features. In addition, the periosteum is proved to be quite site-specific in many ways. This brings challenges to the selection of periosteal donor sites. Limited understanding of the periosteum sets up barriers to developing optimal tissue regeneration strategies. A better understanding of periosteum could lead to better applications. Therefore, we reviewed the histological structure, gene expression, and function of the periosteum from both the commonality and personalization. It aims to discuss some obscure issues and untapped potential of periosteum and artificial periosteum in the application, where further theoretical research is needed. Overall, the site-specificity of the periosteum needs to be fully considered in future applications. However, significant further work is needed in relevant clinical trials to promote the further development of artificial periosteum.