Efficient Transdermal Delivery of DNA Nanostructures Alleviates Atopic Dermatitis Symptoms in NC/Nga Mice

Abstract

AbstractDNA nanostructures have been widely studied in biomedical research contributing to targeted treatment of chronic diseases. The immunostimulatory XL‐DNA nanostructures of X‐shaped oligodeoxynucleotides complex are previously reported, activating toll‐like receptor9 in dendritic cells. This study examines whether the XL‐DNA could be therapeutically applied to treat immune diseases such as atopic dermatitis. To optimize topical delivery, liposome‐encapsulated XL‐DNA (Lipo‐XL‐DNA) is generated using emulsion transfer method with lipid layers composed of 1,2‐dioleoyl‐sn‐glycero‐3‐phosphocholine, 1,2‐dioleoyl‐sn‐glycero‐3‐phospho‐(1′‐rac‐glycerol), and cholesterol. Size distribution of Lipo‐XL‐DNA ranges around 90–160 nm with mean diameter of 115.44 ± 18.72 nm. The morphology is confirmed by transmission electron microscope. Zeta potential is −28.59 mV. Confocal microscopy shows that Lipo‐XL‐DNA is efficiently delivered into epidermis and dermis. Topical application of Lipo‐XL‐DNA effectively alleviates atopic dermatitis symptoms in mice, as shown by dermatitis score, histological evaluation, and serum immunoglobulin E levels. RNA‐seq analysis confirms that Lipo‐XL‐DNA reduces pro‐inflammatory products, but increases epidermal barrier homeostasis factors in atopic dermatitis lesions. Lipo‐XL‐DNA orchestrates immune balance by downregulating Th2 immunity, but upregulating Th1 immunity. Collectively, liposome encapsulation enables efficient transdermal delivery of XL‐DNA, for an effective treatment of atopic dermatitis in mice. The results provide a promising therapeutic strategy using XL‐DNA nanostructures to treat immune‐compromised diseases.