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

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.

Emerging porous organic polymers for biomedical applications

“…Fan et al also reported that the introduction of hydrophilic PEG can improve the dispersibility of POPs in PBS and Opti-MEM cell medium. 116 In addition to modifying POPs with hydrophilic polymers to improve their water dispersibility, introducing flexible moieties into the building blocks would also be an effective approach. Lin et al reported ionic POPs constructed from semirigid tetraaldehyde and flexible dihydrazides.…”

“…Then, a brief discussion on their synthetic strategies and functionalization approaches is provided. Subsequently, a detailed description is provided on the applications of POPs in diverse biomedical fields, including drug delivery, 76,101–116 biomacromolecule encapsulation, 117–129 photodynamic and photothermal therapy, 130–147 biosensing, 69,148–151 bioimaging, 152–155 antibacterial, 156–161 bioseparation, 162 and others, as shown in Fig. 2.…”

Porous organic polymers for drug delivery: hierarchical pore structures, variable morphologies, and biological properties

“…(1) Compared with other soluble and biodegradable polymers, 187,188 the biocompatibility and dispersibility of POPs are still poor to meet the need for treatment. 189,190 Commonly, nanoscale particle sizes 191 and hydrophilicity 192 are important for increasing drug-delivery performance in physiological media. The methods to enhance targeted drug release while reducing damage to healthy cells using functionalized POPs with stimuli-responsive groups require further investigation.…”

2D and 3D Covalent Organic Frameworks: Cutting-Edge Applications in Biomedical Sciences

“…In vitro gene delivery studies in both the HeLa and 293T cells reveal that CTF–PEG-PEI has lower cytotoxicity and good gene transfection performance compared to PEI. The lack of in vivo trial is one of drawbacks of this study . In another study, a cationic COF nanoparticle with good dispersion and uniform size was prepared through the one-pot method.…”

“…The lack of in vivo trial is one of drawbacks of this study. 76 In another study, a cationic COF nanoparticle with good dispersion and uniform size was prepared through the one-pot method. This COF-based gene vector exhibited good biocompatibility and excellent gene transfection ability both in vitro and in vivo.…”