DNA Origami as a Nanomedicine for Targeted Rheumatoid Arthritis Therapy through Reactive Oxygen Species and Nitric Oxide Scavenging

Abstract

Rheumatoid arthritis (RA) severely threatens human health by causing inflammation, swelling, and pain in the joints and resulting in persistent synovitis and irreversible joint disability. In the development of RA, pro-inflammatory M1 macrophages, which express high levels of reactive oxygen species (ROS) and nitric oxide (NO), induce synovial inflammation and bone erosion. Eliminating ROS and NO in the inflamed joints is a potential RA therapeutic approach, which can drive the transition of pro-inflammatory M1 macrophages to the anti-inflammatory M2 phenotype. Taking advantage of the intrinsic ROS- and NO-scavenging capability of DNA molecules, herein, we report the development of folic acid-modified triangular DNA origami nanostructures (FA-tDONs) for targeted RA treatment. FA-tDONs could efficiently scavenge ROS and NO and actively target M1 macrophages, facilitating the M1-to-M2 transition and the recovery of associated cytokines and biomarkers to the normal level. The therapeutic efficacy of FA-tDONs was examined in the RA mouse model. As validated by appearance, histological, and serum examinations, FA-tDONs treatment effectively alleviated synovial infiltration and cartilage damage, attenuating disease progression. This study demonstrated the usage of DNA origami for RA treatment and suggested its potential in other antioxidant therapies.

Recent Advances in DNA Origami-Engineered Nanomaterials and Applications

“…Furthermore, Ma et al developed a folic acid (FA)-decorated DNA origami as nanomedicine for rheumatoid arthritis (RA) therapy. 335 Taking advantage of the efficient ROS-and nitric oxide (NO)-scavenging capability of DNA, the DNA nanostructures worked as antioxidant agents for inflammations. FA molecules in the assemblies were used as targeting ligands for pro-inflammatory M1 macrophages, which predominantly promoted RA progression, including monocyte recruitment, fibroblast proliferation, and pro-inflammatory cytokine secretion.…”

“…Due to their reactive oxygen species (ROS)-scavenging effects, the DON treatment showed preferable renal-protective properties in AKI animals with cell damage caused by local ROS. Furthermore, Ma et al developed a folic acid (FA)-decorated DNA origami as nanomedicine for rheumatoid arthritis (RA) therapy . Taking advantage of the efficient ROS- and nitric oxide (NO)-scavenging capability of DNA, the DNA nanostructures worked as antioxidant agents for inflammations.…”

Arthritic Microenvironment‐Dictated Fate Decisions for Stem Cells in Cartilage Repair

“…There are two enhancement strategies for small molecule drugs: 1) increasing the drug delivery concentration and 2) a drug targeting strategy ( Table 2 ). [ 158–211 ] Andersen et al. attempted to target MTX and siRNA in neutrophils and monocytes using CNTs.…”

“…Ma et al achieved a targeted antioxidant effect with DNA origami drugs. [170] Engineering vesicles have the advantages of immune escape and low immunogenicity. Moreover, they can carry a wide range of molecules and effectively increase the delivered concentration.…”

Inflammation-Responsive Nanoagents for Activatable Photoacoustic Molecular Imaging and Tandem Therapies in Rheumatoid Arthritis

“…In clinical practice, joint radiography, ultrasound, X-ray computed tomography (CT), and magnetic resonance imaging (MRI) are currently available for assessing RA. − However, due to the low sensitivity and specificity, these imaging modalities primarily detect structural changes in joints during the later stages of RA, and are not ideally suited as primary imaging tools for the early diagnosis of RA and monitoring treatment response. Synovial biopsy has also been utilized in some cases to evaluate the histologic characteristics of synovium, which is, however, an invasive and demanding procedure. , Fluorescence imaging has shown promise as an alternative technique for RA detection due to the advantages of high sensitivity and resolution, real-time feedback, radiation-free nature, and ease of operation. − Nevertheless, fluorescence imaging, especially in the visible region and traditional near-infrared (NIR) window, faces limitations in terms of shallow penetration depth and unsatisfied spatial resolution. − Therefore, there is an urgent need to explore a powerful imaging strategy to facilitate the in vivo accurate diagnosis and efficient management of RA.…”