Dual-Functionalized Covalent Triazine Framework Nanosheets as Hierarchical Nonviral Vectors for Intracellular Gene Delivery

Gene therapy is a revolutionary biomedical technique for the treatment of many diseases, and the development of safe and efficient intracellular gene delivery vectors is crucial for successful gene therapy. Herein, we report a strategy to construct dual-functionalized covalent triazine framework-poly(ethylene glycol)-polyethylenimine (CTF-PEG-PEI) nanosheets as nonviral vectors via exfoliation and surface chemistry modification. Benefiting from the unique brushlike hierarchical structure, CTF-PEG-PEI can strongly condense nucleic acids and efficiently release the nucleic acid cargo after cellular uptake. Systematic gene delivery studies in both 293T and HeLa cells demonstrate that CTF-PEG-PEI has superior gene transfection performance and lower cytotoxicity compared with polyethylenimine (PEI), especially at low dosages.