A Ferrocene-Functionalized Covalent Organic Framework for Enhancing Chemodynamic Therapy via Redox Dyshomeostasis.

Chemodynamic therapy (CDT), which induces cell death by decomposing high levels of H2 O2 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.

Covalent Organic Frameworks (COFs) for Cancer Therapeutics.

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.

A Glycosylated Covalent Organic Framework Equipped with BODIPY and CaCO3 for Synergistic Tumor 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 1 O2 . 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 1 O2 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 1 O2 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.

UiO-68-PT MOF-Based Sensor and Its Mixed Matrix Membrane for Detection of HClO in Water.

As an important type of reactive oxygen species (ROS), hypochloric acid (HClO) is closely linked with our daily life, and its convenient and rapid detection is very significant and imperative. Fluorescent and visual probes are being recognized as powerful and convenient tools for detection of ROS in the environment and living organisms by visualizing and imaging. In this contribution, a new metal-organic framework-based fluorescent probe UiO-68-PT, which was generated from a phenthiazine-decorated benzimidazole bridging dicarboxyl ligand and ZrCl4 under solvothermal conditions via in situ one-pot approach, is reported. The obtained UiO-68-PT features a unique HClO and Vitamin C-triggered reversible redox process, which is accompanied by both visual and fluorescence changes. Therefore, it can be a highly sensitive, specific, and reusable sensor to detect HClO species in water via both visual and fluorogenic observation (turn-on). Furthermore, its mixed membrane material (MMM) was fabricated by the combination of UiO-68-PT and poly(vinyl alcohol), and the obtained hydrophilic MMM can be used as a reversible colorimetric card for visual detection of the HClO in aqueous solution.

Three Silver Nests Capped by Thiolate/Phenylphosphonate.

Introducing phenylphosphonic acid (H2 PPA) into the Ag/tBuSH assembly system has produced a family of nanoscale-sized, high-atom number, silver thiolate/PPA nests (SD/Ag45 a, SD/Ag66 a, and SD/Ag73 a) with impressive core-shell features. SD/Ag45 a is a 45-atom ellipsoid comprised of an Ag36 shell trapping an Ag9 S2 three-bladed rotor inside. SD/Ag66 a comprises an inner rod-like Ag20 core and an outer Ag44 shell, giving a 64-atom nest. These Ag64 nests are further extended by Ag(CN)2 linkers to form a one-dimensional chain structure. SD/Ag73 a is a three-shell 73-nucleus silver nest with a central silver atom enclosed in a rhombicuboctahedron of 24 silver atoms, which is itself enclosed in the outermost shell of a rectified version of a 48-Ag octahedral Goldberg 2,0 cage. The solution behaviors and optical absorption properties of the three nests are described in detail. Of note, SD/Ag45 a and SD/Ag73 a emit in the near-infrared region and show different luminescent thermochromic behavior. This work demonstrates that the participation of H2 PPA strongly influences the structures of silver thiolate nests, thus providing a new route to fabricate and modify them in a more rational way.

Benzoate-Induced High-Nuclearity Silver Thiolate Clusters.

Compared with the well-known anion-templated effects in shaping silver thiolate clusters, the influence from the organic ligands in the outer shell is still poorly understood. Herein, three new benzoate-functionalized high-nuclearity silver(I) thiolate clusters are isolated and characterized for the first time in the presence of diverse anion templates such as S2- , α-[Mo5 O18 ]6- , and MoO42- . Single-crystal X-ray analysis reveals that the nuclearities of the three silver clusters (SD/Ag28, SD/Ag29, SD/Ag30) vary from 32 to 38 to 78 with co-capped tBuS- and benzoate ligands on the surface. SD/Ag28 is a turtle-like cluster comprising a Ag29 shell caging a Ag3 S3 trigon in the center, whereas SD/Ag29 is a prolate Ag38 sphere templated by the α-[Mo5 O18 ]6- anion. Upon changing from benzoate to methoxyl-substituted benzoate, SD/Ag30 is isolated as a very complicated core-shell spherical cluster composed of a Ag57 shell and a vase-like Ag21 S13 core. Four MoO42- anions are arranged in a supertetrahedron and located in the interstice between the core and shell. Introduction of the bulky benzoate changes elaborately the nuclearity and arrangements of silver polygons on the shell of silver clusters, which is exemplified by comparing SD/Ag28 and a known similar silver thiolate cluster. The three new clusters emit luminescence in the near-infrared (NIR) region and show different thermochromic luminescence properties. This work presents a flexible approach to synthetic studies of high-nuclearity silver clusters decorated by different benzoates, and structural modulations are also achieved.

Diiodo-Bodipy-Encapsulated Nanoscale Metal-Organic Framework for pH-Driven Selective and Mitochondria Targeted Photodynamic Therapy.

We report herein a new ZIF-90-based PDT agent which was synthesized by in situ assembly of imidazole-2-carboxaldehyde (IcaH), Zn(NO3)2, and heavy atom iodine-attached Bodipy. The obtained 2I-BodipyPhNO2@ZIF-90 (1) host-guest photosensitive system featured low cytotoxicity, good biocompatibility, pH-driven selective cancer cell uptake and release, mitochondria targeting, and highly efficient pH-triggered 1O2 generation. Therefore, it can be used as a high-performing PDT agent to selectively kill tumor cells. In comparison to free 2I-BodipyPhNO2, 1 exhibits a much higher antitumor efficacy and selectivity, which was confirmed by in vitro cell experiments.

One-Pot Synthetic Approach toward Porphyrinatozinc and Heavy-Atom Involved Zr-NMOF and Its Application in Photodynamic Therapy.

Herein, we report an iodine-attached Zn(II)-porphyrinic dicarboxylic building block (ZnDTPP-I2-2H, 1) that can be introduced into UiO-66 NMOF via one-pot synthetic approach to generate a new ZnDTPP-I2 doped UiO-66 type nano metal-organic framework (NMOF) of ZnDTPP-I2⊂UiO-66 (2). Compared to its homologous iodine-free NMOF of ZnDTPP⊂UiO-66 (4), ZnDTPP-I2⊂UiO-66 (2) with heavy iodine atoms is a more effective nanosized photosensitizer for singlet oxygen generation under physiological conditions. As expected, 2 displayed a high photodynamic therapy efficacy for treatment of liver cancer cells in vitro.

CuI@UiO-67-IM: A MOF-Based Bifunctional Composite Triphase-Transfer Catalyst for Sequential One-Pot Azide-Alkyne Cycloaddition in Water.

A CuI-loaded and n-pentadecyl-attached imidazolium salt decorated UiO-67-type metal-organic framework (CuI@UiO-67-IM, 2) based on a new premodified ligand L (n-pentadecyl-attached imidazolium (IM) decorated dicarboxylic acid) and ZrCl4 is reported. Compound 2 can be a bifunctional composite heterogeneous phase-transfer catalyst to promote the azide-alkyne cycloaddition (H2O, air, 80 °C) from corresponding halogenated compounds and sodium azide as a sequential one-pot procedure with high yields and excellent regioselectivity.

UiO-68-ol NMOF-Based Fluorescent Sensor for Selective Detection of HClO and Its Application in Bioimaging.

Fluorescent probes are powerful tools for the investigations of reactive oxygen species (ROS) in living organisms by visualization and imaging. As one of the most important of the natural reactive oxygen species (ROS), hypochlorous acid (HClO) plays a crucial role in various physiological and pathological processes. We report herein a new redox-switchable NMOF of UiO-68-ol via a direct ligand modification approach. The obtained UiO-68-ol NPs, which contains organic-based molecular redox switches, exhibit excellent photophysical properties for biological application and can be highly sensitive and selective fluorescent probes to detect HClO species in living cells.

Bifunctional Imidazolium-Based Ionic Liquid Decorated UiO-67 Type MOF for Selective CO2 Adsorption and Catalytic Property for CO2 Cycloaddition with Epoxides.

A bifunctional robust and highly porous imidazolium-based ionic liquid decorated UiO-67 type MOF (UiO-67-IL, 1) was successfully constructed via solvothermal assembly of the imidazolium-based ligand and Zr(IV) ions. It exhibits a highly selective adsorption for CO2 over CH4 and N2. Furthermore, 1 herein can be used as a highly active heterogeneous catalyst for CO2 cycloaddition with epoxides under atmospheric pressure with or without cocatalyst TBAB (n-Bu4NBr).

Pd@Cu(II)-MOF-Catalyzed Aerobic Oxidation of Benzylic Alcohols in Air with High Conversion and Selectivity.

A new 3D porous Cu(II)-MOF (1) was synthesized based on a ditopic pyridyl substituted diketonate ligand and Cu(OAc)2 in solution, and it features a 3D NbO motif which is determined by the X-ray crystallography. Furthermore, the Pd NPs-loaded hybrid material Pd@Cu(II)-MOF (2) was prepared based on 1 via solution impregnation, and its structure was confirmed by HRTEM, SEM, XRPD, gas adsorption-desorption, and ICP measurement. 2 exhibits excellent catalytic activity (conversion, 93% to >99%) and selectivity (>99% to benzaldehydes) for various benzyl alcohol substrates (benzyl alcohol and its derivatives with electron-withdrawing and electron-donating groups) oxidation reactions in air. In addition, 2 is a typical heterogeneous catalyst, which was confirmed by hot solution leaching experiment, and it can be recycled at least six times without significant loss of its catalytic activity and selectivity.

Cd(II)-MOF: adsorption, separation, and guest-dependent luminescence for monohalobenzenes.

A series of isostructural 2-fold interpenetrating 2D Cd(II)-MOFs, namely G⊂CdL2(OTs)2 (G = THF (1), PhF (2), PhCl (3), PhBr (4), PhI (5), L = 1,2-bis[(3-(pyridin-4-yl)phenoxy]ethane, and OTs(-) = p-toluenesulfonate anion), have been successfully synthesized from the flexible ethylene glycol ether-bridging ligand L and Cd(OTs)2 in solution. The CdL2(OTs)2 framework contains squarelike nonpolar channels, and the encapsulated guest molecules can be removed by heating (150 °C) to generate a guest-free host framework which is able to reversibly adsorb monohalobenzenes PhX (X = F, Cl, Br, I) in the liquid phase under ambient conditions without loss of framework integrity. Furthermore, it can effectively separate these monohalobenzenes and exhibits a clear affinity for monohalobenzenes according to the following order: PhI > PhBr > PhCl > PhF. In addition, PhX⊂CdL2(OTs)2 exhibits guest-dependent luminescence properties.

A Pt nanoenzyme- and BODIPY-loaded nanoscale covalent organic framework for relieving intratumoural hypoxia to enhance photodynamic therapy.

Herein, we report a composite COF material loaded with a Pt nanoenzyme and an organic photosensitizer BODIPY, synthesized via a stepwise post-synthetic modification. The obtained Pt@COF-BDP nanoparticles can efficiently and continuously convert H2O2 to O2, thereby increasing the efficiency of single-linear oxygen production and achieving efficient tumor inhibition.

2,5-Bis[4-methyl-3-(pyridin-3-yl)phenyl]-1,3,4-oxadiazole and its one-dimensional polymeric complex with ZnCl2.

2,5-Bis[4-methyl-3-(pyridin-3-yl)phenyl]-1,3,4-oxadiazole (L), C26H20N4O, forms one-dimensional chains via two types of intermolecular π-π interactions. In catena-poly[[dichloridozinc(II)]-µ-2,5-bis[4-methyl-3-(pyridin-3-yl)phenyl]-1,3,4-oxadiazole], [ZnCl2(C26H20N4O)]n, synthesized by the combination of L with ZnCl2, the Zn(II) centres are coordinated by two Cl atoms and two N atoms from two L ligands. [ZnCl2L]n forms one-dimensional P (plus) and M (minus) helical chains, where the L ligand has different directions of twist. The helical chains stack together via interchain π-π and C-H···π interactions.

A covalent organic framework-based nanoreactor for enhanced photothermal therapy via inhibiting intracellular heat defense systems.

Herein, we report an indocyanine green (ICG)-decorated and glucose oxidase (GOx)-loaded nanoscale composite COF material via 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.

A biodegradable covalent organic framework for synergistic tumor therapy.

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).

A reactive oxygen species-responsive covalent organic framework for tumor combination therapy.

Herein, we report the first reactive oxygen species (ROS)-responsive dithioketal-linked covalent organic framework (COF) for synergetic chemotherapy and photodynamic therapy (PDT) of cancer. The singlet oxygen (1O2)-responsive COF dissociation and DC_AC50 drug release complement and reinforce each other to allow an efficient combination of PDT and chemotherapy.

Encapsulation and sensitization of UV-vis and near infrared lanthanide hydrate emitters for dual- and bimodal-emissions in both air and aqueous media based on a porous heteroatom-rich Cd(II)-framework.

A porous heteroatom-rich Cd(II)-polymeric framework which is generated from an ethylene glycol ether-bridging dicarboxylate ligand L, 4,4'-bipy and Cd(II) ion is reported. It contains one-dimensional tubes (9-11 Å) which are able to trap cationic lanthanide hydrates such as Eu(H(2)O)(8)(3+), Tb(H(2)O)(8)(3+), and Nd(H(2)O)(8)(3+) under ambient conditions to generate Ln(H(2)O)(8)(3+)-loaded materials. In addition, the heteroatom-rich host material can effectively protect and sensitize the encapsulated Ln(3+) emitters in their hydrate form in both air and aqueous media. Furthermore, the dual- and bimodal-emissions are successfully realized by intercalation of the different Ln(3+)-hydrates based on a guest-driven approach.

3,5-Bis{4-[(benzimidazol-1-yl)methyl]phenyl}-4H-1,2,4-triazol-4-amine and its one-dimensional polymeric complex with HgCl2.

The molecule of 3,5-bis{4-[(benzimidazol-1-yl)methyl]phenyl}-4H-1,2,4-triazol-4-amine (L), C(30)H(24)N(8), has an antiperiplanar conformation of the two terminal benzimidazole groups and forms two-dimensional networks along the crystallographic b axis via two types of intermolecular hydrogen bonds. However, in catena-poly[[[dichloridomercury(II)]-µ-3,5-bis{4-[(benzimidazol-1-yl)methyl]phenyl}-4H-1,2,4-triazol-4-amine] dichloromethane hemisolvate], {[HgCl(2)(C(30)H(24)N(8))]·0.5CH(2)Cl(2)}(n), synthesized by the combination of L with HgCl(2), the L ligand adopts a synperiplanar conformation. The Hg(II) cation lies in a distorted tetrahedral environment, which is defined by two N atoms and two Cl atoms to form a one-dimensional zigzag chain. These zigzag chains stack via hydrogen bonds which expand the dimensionality of the structure from one to two.