Framework Doping Enhances COF-DNA Nanoplatforms for Dual RNA Imaging and Phototherapy

DNA-engineered covalent organic frameworks (COFs) hold great promise for cancer theranostics. However, regulating the interaction between COFs and functional DNAs remains a significant challenge, despite its crucial role in ensuring the theranostic performance. In this study, we present a framework doping strategy that simultaneously optimizes the diagnostic imaging and phototherapeutic effects of the COF-DNA nanosystems. In situ doping of porphyrin allows the photocatalytic generation of reactive oxygen species (ROS) by COF nanoparticles and facilitates the adsorption and quenching of fluorescent single-stranded DNA (ssDNA). This enabled the construction of a high-performance COF-DNA nanosystem for RNA-imaging guided phototherapy: the system restored intense fluorescence signals in response to cancer-associated mRNA and miRNA and generated abundant ROS upon laser irradiation, thereby simultaneously lighting up and killing cancer cells. The developed framework doping strategy provides valuable insights into regulating COF-DNA interactions and constructing high-performance theranostic nanosystems.