DNA Tetrahedron Functionalized Microneedles Blocking IL-6 to Promote Skin Wound Healing

Excessive secretion of Interleukin-6 (IL-6) is a critical barrier to the healing of inflammatory wounds. Previous attempts aimed to overcome this challenge by using antibodies to neutralize IL-6. However, the immunogenicity of an antibody may trigger antidrug antibody formation, resulting in reduced therapeutic efficacy and possible adverse reactions. In contrast, aptamers (Ap) exhibit better target specificity and anti-inflammatory performance, and have wide applications. Recently, tetrahedral framework nucleic acids (tFNAs) have emerged as promising drug delivery platforms that provide nanomedicines with enhanced stability and tissue penetration. In this work, we first modified IL-6 aptamers onto tFNAs (tFNAs Ap), and then the tFNAs Ap was embedded into the hydrogel microneedle to form a skin dressing (tFNAs Ap MN). These hydrogel microneedles present excellent mechanical strength, swelling capacity, and good biocompatibility, which show significant anti-inflammatory and wound-healing outcomes by inhibiting the regulation of inflammatory factors IL-6 and TNF-α and promoting keratinocyte proliferation and migration. The results of animal experiments indicate that such microneedles suppress the excessive expression of IL-6 efficiently and significantly reduce the time required for healing full-thickness skin wound models with inflammation. Overall, the prepared the DNA materials functionalized microneedles may have potential clinical value in inflammation treatment and wound healing.