Self‐Assembled DNA Nanospheres Driven by Carbon Dots for MicroRNAs Imaging in Tumor via Logic Circuit

DNA nanostructures with diverse biological functions have made significant advancements in biomedical applications. However, a universal strategy for the efficient production of DNA nanostructures is still lacking. In this work, a facile and mild method is presented for self-assembling polyethylenimine-modified carbon dots (PEI-CDs) and DNA into nanospheres called CANs at room temperature. This makes CANs universally applicable to multiple biological applications involving various types of DNA. Due to the ultra-small size and strong cationic charge of PEI-CDs, CANs exhibit a dense structure with high loading capacity for encapsulated DNA while providing excellent stability by protecting DNA from enzymatic hydrolysis. Additionally, Mg²⁺ is incorporated into CANs to form Mg@CANs which enriches the performance of CANs and enables subsequent biological imaging applications by providing exogenous Mg²⁺. Especially, a DNAzyme logic gate system that contains AND and OR Mg@CANs is constructed and successfully delivered to tumor cells in vitro and in vivo. They can be specifically activated by endogenic human apurinic/apyrimidinic endonuclease 1 and recognize the expression levels of miRNA-21 and miRNA-155 at tumor sites by logic biocomputing. A versatile pattern for delivery of diverse DNA and flexible logic circuits for multiple miRNAs imaging are developed.