Dual-Functionalized Covalent Triazine Framework Nanosheets as Hierarchical Nonviral Vectors for Intracellular Gene Delivery
Yaqi Cao, Junshi Zhang, Lan Wang, Mingjun Cen, Wenchao Peng, Yang Li, Fengbao Zhang, Juan Tan, Xiaobin Fan
Abstract
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.