As newly emerged crystalline porous materials, covalent organic frameworks (COFs) possess fascinating structures and some specific features such as modularity, crystallinity, porosity, stability, ...versatility, and biocompatibility. Besides adsorption/separation, sensing, catalysis, and energy applications, COFs have recently shown a promise in biomedical applications. This contribution provides an overview of the recent developments of COF‐based medicines in cancer therapeutics, including drug delivery, photodynamic therapy (PDT), photothermal therapy (PTT), and combined therapy. Furthermore, the major challenges and developing trends in this field are also discussed. These recent developments are summarized and discussed to help encourage further contributions in this emerging and promising field.
Magic bullet: In this minireview, recent advances in the field of covalent organic frameworks (COFs) for cancer therapeutic applications are highlighted, including those for drug delivery, phototherapy, and combined therapy.
Ca2+, a ubiquitous but nuanced modulator of cellular physiology, is meticulously controlled intracellularly. However, intracellular Ca2+ regulation, such as mitochondrial Ca2+ buffering capacity, can ...be disrupted by 1O2. Thus, the intracellular Ca2+ overload, which is recognized as one of the important cell pro‐death factors, can be logically achieved by the synergism of 1O2 with exogenous Ca2+ delivery. Reported herein is a nanoscale covalent organic framework (NCOF)‐based nanoagent, namely CaCO3@COF‐BODIPY‐2I@GAG (4), which is embedded with CaCO3 nanoparticle (NP) and surface‐decorated with BODIPY‐2I as photosensitizer (PS) and glycosaminoglycan (GAG) targeting agent for CD44 receptors on digestive tract tumor cells. Under illumination, the light‐triggered 1O2 not only kills the tumor cells directly, but also leads to their mitochondrial dysfunction and Ca2+ overload. An enhanced antitumor efficiency is achieved via photodynamic therapy (PDT) and Ca2+ overload synergistic therapy.
A multifunctional COF‐based nanoagent, which is equipped with BODIPY‐2I photosensitizer, CaCO3 nanoparticle, and glycosaminoglycan (GAG) targeting agent, can be a highly efficient and selective antitumor nanomedicine for colon tumor via photodynamic therapy (PDT) and Ca2+ overload synergistic therapy.
Chemodynamic therapy (CDT), which induces cell death by decomposing high levels of H2O2 in tumor cells into highly toxic ·OH, is recognized as a promising antineoplastic approach. However, current ...CDT approaches are often restricted by the highly controlled and upregulated cellular antioxidant defense. To enhance ·OH‐induced cellular damage by CDT, a covalent organic framework (COF)‐based, ferrocene (Fc)‐ and glutathione peroxidase 4 (GPX4) inhibitor‐loaded nanodrug, RSL3@COF–Fc (2b), is fabricated. The obtained 2b not only promotes in situ Fenton‐like reactions to trigger ·OH production in cells, but also attenuates the repair mechanisms under oxidative stress via irreversible covalent GPX4 inhibition. As a result, these two approaches synergistically result in massive lipid peroxide accumulation, subsequent cell damage, and ultimately ferroptosis, while not being limited by intracellular glutathione. It is believed that this research provides a paradigm for enhancing reactive oxygen species‐mediated oncotherapy through redox dyshomeostasis and may provide new insights for developing COF‐based nanomedicine.
Versatile covalent organic frameworks (COFs)! The organic nanodrug RSL3@COF–Fc (2b), which integrates the glutathione peroxidase 4 inhibitor RSL3 and Fenton‐like reaction catalyst ferrocene (Fc) into a nanoscale COF, induces ferroptosis to enhance chemodynamic therapy by blocking lipid repair and disrupting cellular redox homeostasis.
It is desirable but challenging to design noble-metal-free photocatalysts with improved activity for hydrogen (H2) evolution. In this study, we fabricated hollow hexagonal porous micro-rods assembled ...from core–shell In2O3@carbon nanoparticles (PHIC) via one-step thermal decomposition of the In-MIL-68 precursor. Under simulated sun-light illumination, the final H2 yield rate of PHIC is comparable to that of Pt/PHI (PHI, hollow hexagonal micro-rods assembled from In2O3 nanoparticles without a carbon layer), indicating that the continuous carbon layer coating on In2O3 nanoparticles has a Pt-like effect on improving the photocatalytic activity. Our experimental results indicated that the improved photocatalytic H2 evolution of PHIC is attributed to the synergistic effect of efficient separation of photo-generated electron–hole pairs caused by the coating carbon layer, the enhanced optical absorption of the hollow structure, and the improved accessibility provided by the porous structure. Among them, efficient separation of photo-generated electron–hole pairs plays the main role. Furthermore, we reveal the microscopic charge carrier migration path via In2O3/graphite interfaces, meaning that the photo-generated electrons from In2O3 O2p orbitals transfer into the carbon C2p orbitals, leaving the photo-generated holes in In2O3 O2p orbitals, which is beneficial to improve the separation of photo-generated electron–hole pairs.
Chronic wound infections resulting from severe bacterial invasion have become a major medical threat worldwide. Herein, we report a large-area, homogeneous, and self-standing porphyrin-covalent ...organic framework (COF)-based membrane with encapsulated ibuprofen (IBU) via an in situ interfacial polymerization and impregnation approach. The obtained IBU@DhaTph-membrane exhibits highly effective antibacterial and anti-inflammatory effects via synergistic light-induced singlet oxygen (
O
) generation and controllable IBU release, which is well supported by in vitro experiments. In addition, the IBU@DhaTph-membrane-based biocompatible "band-aid" type dressing is fabricated, and its excellent anti-infection and tissue remodeling activities are fully evidenced by in vivo chronic wound-healing experiments. This study may inspire and promote the fabrication of many more new types of COF-based multifunctional biomaterials for various skin injuries in clinical medicine.
Herein, we report a microporous carbon nanomaterial that was generated from a nanoscale covalent organic framework precursor
via
a simple pyrolysis approach. The obtained carbon-based nanoparticles ...possessed a broad NIR absorption capacity and exhibited a high level of photothermal conversion ability (
η
= 50.6%) in the NIR-II biowindow. Its excellent PTT antitumor efficiency was fully evidenced by
in vitro
and
in vivo
experiments under 1064 nm laser irradiation.
A nanoscale carbon nanomaterial was synthesized through pyrolysis of its NCOF precursor, and the obtained carbon nanoparticles (CNPs) can be highly efficient NIR-II photothermal agents for antitumor treatment
via
PTT.
Herein, we report an inorganic photothermal agent, CuS- and an organic photosensitizer, BODIPY-loaded composite nanoscale COF material
via
a stepwise post-synthetic modification. The obtained ...CuS@COF-BDP can be a dual-modal therapeutic agent to highly inhibit MCF-7 tumor cell proliferation due to its efficient singlet oxygen generation and photothermal conversion abilities.
A COF-based multifunctional nanomedicine CuS@COF-BDP, which can be used as a PTT/PDT bimodal therapeutic agent to inhibit cancer cell proliferation under visible- and NIR-II-light irradiation, is reported.
Stimulus-responsive biodegradable nanocarriers with tumor-selective targeted drug delivery are critical for cancer therapy. Herein, we report for the first time a redox-responsive disulfide-linked ...porphyrin covalent organic framework (COF) that can be nanocrystallized by glutathione (GSH)-triggered biodegradation. After loading 5-fluorouracil (5-Fu), the generated nanoscale COF-based multifunctional nanoagent can be further effectively dissociated by endogenous GSH in tumor cells, releasing 5-Fu efficiently to achieve selective chemotherapy on tumor cells. Together with the GSH depletion-enhanced photodynamic therapy (PDT), an ideal synergistic tumor therapy for MCF-7 breast cancer
via
ferroptosis is achieved. In this research, the therapeutic efficacy was significantly improved in terms of enhanced combined anti-tumor efficiency and reduced side effects by responding to significant abnormalities such as high concentrations of GSH in the tumor microenvironment (TME).
Stimulus-responsive biodegradable nanocarriers with tumor-selective targeted drug delivery are critical for cancer therapy.
Herein, we report an indocyanine green (ICG)-decorated and glucose oxidase (GOx)-loaded nanoscale composite COF material
a stepwise post-synthetic modification. The obtained GOx@COF-ICG can achieve ...synergistic inhibition of intracellular heat defense systems through starvation therapy to enhance photothermal therapy of tumors.
We demonstrate herein an effective cascade reaction for combined photodynamic and starvation therapy in treating breast tumors based on a photosensitizer and CO prodrug decorated NMOF. The ...PDT-induced ROS can further trigger CO release, and the high antitumor efficiency derived from both
1
O
2
and CO is well confirmed by
in vitro
assays and
in vivo
trials.
The valid combination of photodynamic and starvation therapy was achieved
via
the intracellular cascade reactions on a multifunctional MOF-nanoplatform.
