Acute lung injury (ALI) is characterized by severe inflammation and damage to the lung air–blood barrier, resulting in respiratory function damage and life‐threatening outcomes. Macrophage polarization plays an essential role in the occurrence, development, and outcome of ALI. As drug carriers, self‐assembled DNA nanostructures can potentially overcome the drawbacks and limitations of traditional anti‐inflammatory agents owing to their nontoxicity, programmability, and excellent structural control at the nanoscale. A small interfering RNA (siRNA) and drug dual therapy nanoplatform are proposed and constructed here to combat ALI. The nanoplatform consists of a spermidine‐assembled DNA tetrahedron and four mammalian target of rapamycin siRNAs. Spermidine serves as a mediator of drug delivery vehicle synthesis and a drug that alters macrophage polarization. Both spermidine and siRNA exert anti‐inflammatory effects in vitro and in vivo by regulating the macrophage phenotype. More importantly, these factors exhibit a synergistic anti‐inflammatory effect by promoting macrophage autophagy. For the first time, an anti‐inflammatory dual therapy strategy that uses self‐assembled DNA nanostructures as nontoxic, programmable delivery vehicles is proposed and demonstrated through this work. Future work on utilizing DNA nanostructures for the treatment of noncancerous diseases such as ALI is highly promising and desirable.

Complexing self-assembled DNA nanostructures with various functional guest species is the key to unlocking new and exciting biomedical applications. Cationic guest species not only induce magnesium-free DNA to self-assemble into defined structures but also endow the final complex nanomaterials with new properties. Herein, we propose a novel strategy that employs naturally occurring cationic amino acids to induce DNA self-assembly into defined nanostructures. Natural l -arginine and l -lysine can readily induce the assembly of tile-based DNA nanotubes and DNA origami sheets in a magnesium-free manner. The self-assembly processes are demonstrated to be pH- and concentration-dependent and are achieved at constant temperatures. Moreover, the assembled DNA/amino acid complex nanomaterials are stable at a physiological temperature of 37 °C. Substituting l -arginine with its D form enhances its serum stability. Further preliminary examination of this complex nanomaterial platform for biomedical applications indicates that DNA/amino acids exhibit distinct cellular uptake behaviors compared with their magnesium-assembled counterparts. The nanomaterial mainly clusters around the cell membrane and might be utilized to manipulate molecular events on the membrane. Our study suggests that the properties of DNA nanostructures can be tuned by complexing them with customized guest molecules for a designed application. The strategy proposed herein might be promising to advance the biomedical applications of DNA nanostructures.

Target double-stranded DNA (dsDNA) or single-stranded DNA (ssDNA) can activate the trans-cleavage activity of the CRISPR/Cas12a, cutting the surrounding non-target ssDNA arbitrarily. In typical CRISPR/Cas12a system, this non-target ssDNA with...

Simple, rapid, and highly sensitive methods for single-stranded nucleic acid detection are of great significance in clinical testing. While common methods are inseparable from the participation of enzymes, which greatly...