AIEgen-Based sp² Carbon-Conjugated Covalent Organic Frameworks with High Stability and Emission for Activatable Imaging and Ferroptosis in Target Tumor Cells

Abstract

Synthesis of highly stable and emissive covalent organic frameworks (COFs) for biological applications is urgently needed. Herein, we developed a novel AIEgen-based sp 2 carbonconjugated COF (sp 2 c-COF) for activatable imaging and ferroptosis in target tumor cells. The sp 2 c-COF TFBE-PDAN was obtained by employing tetra-(4-aldehyde-(1,1-biphenyl)) ethylene (TFBE) as an AIEgen unit and 1,4-phenylenediacetonitrile (PDAN) as a linker through the Knoevenagel reaction. The asobtained COF TFBE-PDAN exhibited high chemical stability even in 3 M HCl and 3 M NaOH and 146-fold quantum yield enhancement compared with the corresponding imine-linked COF due to the C�C linkages and the AIEgens. The luminescence of COF TFBE-PDAN was dramatically quenched by a tannic acid (TA)based metal phenolic network (Fe III TA), which was formed via Fe(III)-directed metal−polyphenol coordination. After modified with polyethylenimine (PEI), COF TFBE-PDAN @Fe III TA-PEI was used for activatable imaging and ferroptosis. Fe III TA was dissociated in overexpressed glutathione (GSH) and the acidic lysosomal environment, which resulted in the recovery of luminescence and in situ Fe 2+ production. Overloaded H 2 O 2 in tumor cells could further react with Fe 2+ to produce reactive oxygen species (ROS) via the Fenton reaction. GSH depletion and ROS production led to lipid peroxide accumulation-mediated ferroptosis. The luminescence recovery of COF TFBE-PDAN also enabled it to act as a selfreporter for the decomposition of Fe III TA and imaging in tumor cells. This study shows that AIEgen-based sp 2 c-COF displays great potential for tumor cell imaging and therapy.

Covalent Organic Frameworks: Recent Progress in Biomedical Applications

“…Synthetic route to sp 2 c-COF TFBE‑PDAN and COF TFBE‑PDAN @Fe III TA-PEI nanoparticles. Adapted with permission from ref . Copyright 2022 American Chemical Society.…”

“…(a) LSM images of MCF-7 and MCF-10A cells after incubation with 40 μg mL –1 COF TFBE‑PDAN @Fe III TA-PEI at different times. (b) LSM images of AO-stained MCF-7 and MCF-10A cells incubated with or without 80 μg mL –1 COF TFBE‑PDAN @Fe III TA-PEI for 48 h. Adapted with permission from ref . Copyright 2022 American Chemical Society.…”

“…139 Benefiting from their porous feature and modifiable skeletons, COFs with intrinsic fluorescence, hybridized with fluorescence, or with strong fluorescence quenching performance have been demonstrated as promising candidates for fluorescent imaging. 140 In 2022, You et al 141 developed an AIEgen-based sp 2 carbon-conjugated COF (sp 2 c-COF TFBE-PDAN ) via a Knoevenagel reaction between 1,4-phenylenediacetonitrile (PDAN) and AIE-active unit tetra-[4-aldehyde-(1,1-biphenyl)] ethylene (TFBE), where tannic acid was attached on the surface of the COF via hydrophobic interaction, hydrogen bond, and π−π stacking (Figure 22). 141 The grafted tannic acid cross-linked with Fe 3+ through metal− polyphenol coordination bonds to quench the luminescence of COF TFBE-PDAN via energy transfer between tetra-[4-aldehyde-(1,1-biphenyl)]ethylene and 1,4-phenylenediacetonitrile.…”

“…140 In 2022, You et al 141 developed an AIEgen-based sp 2 carbon-conjugated COF (sp 2 c-COF TFBE-PDAN ) via a Knoevenagel reaction between 1,4-phenylenediacetonitrile (PDAN) and AIE-active unit tetra-[4-aldehyde-(1,1-biphenyl)] ethylene (TFBE), where tannic acid was attached on the surface of the COF via hydrophobic interaction, hydrogen bond, and π−π stacking (Figure 22). 141 The grafted tannic acid cross-linked with Fe 3+ through metal− polyphenol coordination bonds to quench the luminescence of COF TFBE-PDAN via energy transfer between tetra-[4-aldehyde-(1,1-biphenyl)]ethylene and 1,4-phenylenediacetonitrile. Then, polyethylenimine (PEI) was modified onto the surface of COF TFBE-PDAN @Fe III TA to facilitate COFTFBE-PDAN@FeIII-TA nanoparticles accessing cells.…”

Solvatochromic Near-Infrared Aggregation-Induced Emission-Active Acrylonitriles by Acceptor Modulation for Low-Power Stimulated Emission Depletion Nanoscopy

“…Donor–acceptor (D-A)-based acrylonitriles have emerged as a new scaffold to construct diverse functional AIEgens with excellent photostability for biological applications because of their facile synthesis and easy purification. − In general, long-wavelength emissive acrylonitriles can be prepared by the extension of the π-conjugation and introduction of strong donor and acceptor units . Unfortunately, these strategies typically render strong hydrophobicity to the fluorophores, leading to poor cell permeability.…”