Facilitating Macrophage Uptake of DNA Nanostructures for Integrated Imaging and Therapy of Acute Respiratory Distress Syndrome

Acute respiratory distress syndrome (ARDS) is a life-threatening inflammatory disorder. While supportive care has improved, mortality remains high. So better diagnostics and targeted therapies are necessary. Tetrahedral DNA (TET) has been widely studied and applied in fields such as biosensors, drug delivery, and bioimaging. However, the cellular internalization capacity of traditional TET remains limited, which makes it challenging to apply TET for imaging or drug delivery inside cells. Here, we found that polyG modified on TET can promote it to be internalized into macrophages significantly. Based on this, we have achieved high-sensitivity imaging of miR-155 in macrophages and anti-inflammatory treatment for ARDS through synthesizing multifunctional TETs. When imaging miR-155, we created a multifunctional tetrahedral DNA (TET-H₁H₂2G(14)) with polyG and two hairpins on its vertices. Using this method, we have achieved ultrasensitive and specific imaging of miR-155 in macrophages and an ARDS mouse model. Besides, we have achieved anti-inflammatory effects in an ARDS mouse model by transporting antisense nucleic acid for miR-155 through TET modified with polyG. In total, we found that modifying polyG on TET can significantly promote its entry into macrophages and further demonstrated its application in bioimaging and drug delivery by synthesizing multiple multifunctional TETs.