Tunable Wettability of a Dual-Faced Covalent Organic Framework Membrane for Enhanced Water Filtration.

Membrane technology plays a central role in advancing separation processes, particularly in water treatment. Covalent organic frameworks (COFs) have transformative potential in this field due to their adjustable structures and robustness. However, conventional COF membrane synthesis methods are often associated with challenges, such as time-consuming processes and limited control over surface properties. Our study demonstrates a rapid, microwave-assisted method to synthesize self-standing COF membranes within minutes. This approach allows control over the wettability of the surface and achieves superhydrophilic and near-hydrophobic properties. A thorough characterization of the membrane allows a detailed analysis of the membrane properties and the difference in wettability between its two faces. Microwave activation accelerates the self-assembly of the COF nanosheets, whereby the thickness of the membrane can be controlled by adjusting the time of the reaction. The superhydrophilic vapor side of the membrane results from -NH2 reactions with acetic acid, while the nearly hydrophobic dioxane side has terminal aldehyde groups. Leveraging the superhydrophilic face, water filtration at high water flux, complete oil removal, increased rejection with anionic dye size, and resistance to organic fouling were achieved. The TTA-DFP-COF membrane opens new avenues for research to address the urgent need for water purification, distinguished by its synthesis speed, simplicity, and superior separation capabilities.

Ionic Covalent Organic Framework as a Dual Functional Sensor for Temperature and Humidity.

Visual sensing of humidity and temperature by solids plays an important role in the everyday life and in industrial processes. Due to their hydrophobic nature, most covalent organic framework (COF) sensors often exhibit poor optical response when exposed to moisture. To overcome this challenge, the optical response is set out to improve, to moisture by incorporating H-bonding ionic functionalities into the COF network. A highly sensitive COF, consisting of guanidinium and diformylpyridine linkers (TG-DFP), capable of detecting changes in temperature and moisture content is fabricated. The hydrophilic nature of the framework enables enhanced water uptake, allowing the trapped water molecules to form a large number of hydrogen bonds. Despite the presence of non-emissive building blocks, the H-bonds restrict internal bond rotation within the COF, leading to reversible fluorescence and solid-state optical hydrochromism in response to relative humidity and temperature.

Covalent Organic Framework Embedded with Magnetic Nanoparticles for MRI and Chemo-Thermotherapy.

Nanoscale imine-linked covalent organic frameworks (nCOFs) were first loaded with the anticancer drug Doxorubicin (Dox), coated with magnetic iron oxide nanoparticles (γ-Fe2O3 NPs), and stabilized with a shell of poly(l-lysine) cationic polymer (PLL) for simultaneous synergistic thermo-chemotherapy treatment and MRI imaging. The pH responsivity of the resulting nanoagents (γ-SD/PLL) allowed the release of the drug selectively within the acidic microenvironment of late endosomes and lysosomes of cancer cells (pH 5.4) and not in physiological conditions (pH 7.4). γ-SD/PLL could efficiently generate high heat (48 °C) upon exposure to an alternating magnetic field due to the nCOF porous structure that facilitates the heat conduction, making γ-SD/PLL excellent heat mediators in an aqueous solution. The drug-loaded magnetic nCOF composites were cytotoxic due to the synergistic toxicity of Dox and the effects of hyperthermia in vitro on glioblastoma U251-MG cells and in vivo on zebrafish embryos, but they were not significantly toxic to noncancerous cells (HEK293). To the best of our knowledge, this is the first report of multimodal MRI probe and chemo-thermotherapeutic magnetic nCOF composites.

Aqueous Synthesis of Triphenylphosphine-Modified Gold Nanoparticles for Synergistic In Vitro and In Vivo Photothermal Chemotherapy.

Triphenylphosphine (TPP) surface-functionalized and F-108 Pluronic-stabilized gold nanoparticles (F-108@TPP-AuNPs) have been synthesized through a one-step approach, leading to well-defined (9.6±1.6 nm) and water-soluble nanoparticles by microwave heating an aqueous solution of TPP-AuI Cl in the presence of a Pluronic polymer under basic conditions. TPP release was negligible under physiological conditions, but enhanced significantly at an acidic pH (5.4) mimicking that of a cancer cell. Laser irradiation (532 nm) raised the temperature of an aqueous solution of F-108@TPP-AuNPs to 51.7 °C within 5 min, confirming efficient light-to-heat conversion capabilities without significant photodegradation. TEM confirmed intracellular localization of F-108@TPP-AuNPs in the cytosol, endosomes and lysosomes of HeLa cells. F-108@TPP-AuNPs were well tolerated by HeLa cells and zebrafish embryos at ambient temperatures and became toxic upon heat activation, suggesting synergistic interactions between heat and cytotoxic action by TPP.

pH-controlled preferential binding of cucurbit[7]uril-coated iron-oxide nanoparticles to 6-mercaptonicotinic acid for fluorescent detection of cadmium ions in the solid state.

A host-guest complex of 6-mercaptonicotinic acid (MNA) and cucurbit[7]uril (CB7) was prepared and conjugated to γ-Fe3O4 nanoparticles (NPs) to detect toxic cadmium ions in water as a solid-state sensor. The formation of an inclusion host-guest complex with CB7 was confirmed by UV-vis absorption and proton NMR spectroscopy. CB7 preferentially binds the protonated MNA form compared to the neutral form, demonstrated by a binding constant for the protonated form that is four orders of magnitude higher than that of the neutral form. An increase in the pKa of MNA by 1.2 units was demonstrated after the addition of CB7, which further supports preferential binding between MNA and CB7. The NMR results confirm binding to cadmium via the carboxylic acid moiety. Stationary and time-resolved fluorescence results, in solution and in the solid state, indicate that cadmium and CB7 cause a blue shift in the MNA emission bands and extend its excited-state lifetime due to dissociation of the MNA dimer. In the solid state, switching the emission signals between Cd2+-MNA/CB7NPs (ON state) and MNAH+/CB7NPs (OFF state) was achieved by controlling the pH. An efficient, regenerable, and stable sensor device was fabricated for sensitive and selective detection of Cd2+ in contaminated water samples. Graphical abstract Regeneration of MNA/CB7 nanoparticles for the detection of cadmium ions in the solid state by a visible blue emission signal upon suppression of photoinduced electron transfer (PET).

Hollow micro and nanostructures for therapeutic and imaging applications.

Hollow particles have been extensively used in bioanalytical and biomedical applications for almost two decades due to their unique and tunable optoelectronic properties as well as their significantly high loading capacities. These intrinsic properties led them to be used in various bioimaging applications as contrast agents, controlled delivery (i.e. drugs, nucleic acids and other biomolecules) platforms and photon-triggered therapies (e.g. photothermal and photodynamic therapies). Since recent studies showed that imaging-guided targeted therapeutics have higher success rates, multimodal theranostic platforms (combination of one or more therapy and diagnosis modality) have been employed more often and hollow particles (i.e. nanoshells) have been one of the most efficient candidates to be used in multiple-purpose platforms, owing to their intrinsic properties that enable synergistic multimodal performance. In this review, recent advances in the applications of such hollow particles fabricated with various routes (either inorganic or organic based) were summarized to delineate strategies for tuning their properties for more efficient biomedical performance by overcoming common biological barriers. This review will pave the ways for expedited progress in design of next generation of hollow particles for clinical applications.

Palladium-Loaded Cucurbit[7]uril-Modified Iron Oxide Nanoparticles for C-C Cross-Coupling Reactions.

Cucurbit[7]uril modified iron oxide nanoparticles (CB[7]NPs) were loaded with palladium to form nano-catalysts (Pd@CB[7]NPs) that, with microwave heating, catalysed Suzuki-Miyaura, Sonogashira, and Mizoroki-Heck cross-coupling reactions. Reactions were run in environmentally benign 1:1 ethanol/water solvent under convenient aerobic conditions. In a preliminary screening, conversions and yields were uniformly high with turn over frequencies (TOF) ranging from 64 to 7360 h-1 . The nano-catalysts could be recovered with a magnet and reused several times (6 times for Suzuki-Miayura reaction) without loss of activity.

Design of Organic Macrocycle-Modified Iron Oxide Nanoparticles for Drug Delivery.

Paul Ehrlich's vision of a "magic bullet" cure for disease inspires the modern design of nanocarriers whose purpose is to deliver drug cargo to specific sites in the body while circumventing endogenous immunological clearance mechanisms. Iron oxide nanoparticles (IONPs) have emerged as particularly promising nanocarriers because of their biodegradability, ability to be guided magnetically to sites of pathology, mediation of hyperthermic therapy, and imaging capabilities. In this review, we focus on the design and drug-delivery aspects of IONPs coated with organic macrocycles (crown ethers, cyclodextrins, calix[n]arenes, cucurbit[n]urils, or pillar[n]arenes), which, by means of reversible complexation, allow for the convenient loading and release of drug molecules. Macrocycles can be attached to IONPs indirectly or directly. Indirect attachment requires the use of small organic linking molecules or conjugation to shell materials. Direct attachment requires neither. We discuss in detail drug release from the macrocycles, highlighting mechanisms that depend on external stimuli such as changes in pH, the competitive binding of ions or small molecules, or the application of ultrasound or electromagnetic radiation.

Mesoporous γ-Iron Oxide Nanoparticles for Magnetically Triggered Release of Doxorubicin and Hyperthermia Treatment.

Mesoporous iron-oxide nanoparticles (mNPs) were prepared by using a modified nanocasting approach with mesoporous carbon as a hard template. mNPs were first loaded with doxorubicin (Dox), an anticancer drug, and then coated with the thermosensitive polymer Pluronic F108 to prevent the leakage of Dox molecules from the pores that would otherwise occur under physiological conditions. The Dox-loaded, Pluronic F108-coated system (Dox@F108-mNPs) was stable at room temperature and physiological pH and released its Dox cargo slowly under acidic conditions or in a sudden burst with magnetic heating. No significant toxicity was observed in vitro when Dox@F108-mNPs were incubated with noncancerous cells, a result consistent with the minimal internalization of the particles that occurs with normal cells. On the other hand, the drug-loaded particles significantly reduced the viability of cervical cancer cells (HeLa, IC50 =0.70 µm), wild-type ovarian cancer cells (A2780, IC50 =0.50 µm) and Dox-resistant ovarian cancer cells (A2780/AD, IC50 =0.53 µm). In addition, the treatment of HeLa cells with both Dox@F108-mNPs and subsequent alternating magnetic-field-induced hyperthermia was significantly more effective at reducing cell viability than either Dox or Dox@F108-mNP treatment alone. Thus, Dox@F108-mNPs constitute a novel soft/hard hybrid nanocarrier system that is highly stable under physiological conditions, temperature-responsive, and has chemo- and thermotherapeutic modes of action.

Redox-Responsive Viologen-Mediated Self-Assembly of CB[7]-Modified Patchy Particles.

Sulfonated surface patches of poly(styrene)-based colloidal particles (CPs) were functionalized with cucurbit[7]uril (CB[7]). The macrocycles served as recognition units for diphenyl viologen (DPV(2+)), a rigid bridging ligand. The addition of DPV(2+) to aqueous suspensions of the particles triggered the self-assembly of short linear and branched chainlike structures. The self-assembly mechanism is based on hydrophobic/ion-charge interactions that are established between DPV(2+) and surface-adsorbed CB[7]. DPV(2+) guides the self-assembly of the CPs by forming a ternary DPV(2+)⊂(CB[7])2 complex in which the two CB[7] macrocycles are attached to two different particles. Viologen-driven particle assembly was found to be both directional and reversible. Whereas sodium chloride triggers irreversible particle disassembly, the one-electron reduction of DPV(2+) with sodium dithionite causes disassembly that can be reversed via air oxidation. Thus, this bottom-up synthetic supramolecular approach allowed for the reversible formation and directional alignment of a 2D colloidal material.

Viologen-templated arrays of cucurbit[7]uril-modified iron-oxide nanoparticles.

Magnetic and fluorescent assemblies of iron-oxide nanoparticles (NPs) were constructed by threading a viologen-based ditopic ligand, DPV(2+), into the cavity of cucurbituril (CB[7]) macrocycles adsorbed on the surface of the NPs. Evidence for the formation of 1:2 inclusion complexes that involve DPV(2+) and two CB[7] macrocycles was first obtained in solution by (1)H NMR and emission spectroscopy. DPV(2+) was found to induce self-assembly of nanoparticle arrays (DPV(2+)⊂CB[7]NPs) by bridging CB[7] molecules on different NPs. The resulting viologen-crosslinked iron-oxide nanoparticles exhibited increased saturation magnetization and emission properties. This facile supramolecular approach to NP self-assembly provides a platform for the synthesis of smart and innovative materials that can achieve a high degree of functionality and complexity and that are needed for a wide range of applications.

Effects of subcutaneous vs. oral nanoparticle-mediated insulin delivery on hemostasis disorders in type 1 diabetes: A rat model study.

Complications associated with Type 1 diabetes (T1D) have complex origins that revolve around chronic hyperglycemia; these complications involve hemostasis disorders, coagulopathies, and vascular damage. Our study aims to develop innovative approaches to minimize these complications and to compare the outcomes of the new approach with those of traditional methods. To achieve our objective, we designed novel nanoparticles comprising covalent organic frameworks (nCOF) loaded with insulin, termed nCOF/Insulin, and compared it to subcutaneous insulin to elucidate the influence of insulin delivery methods on various parameters, including bleeding time, coagulation factors, platelet counts, cortisol plasma levels, lipid profiles, and oxidative stress parameters. Traditional subcutaneous insulin injections exacerbated hemostasis disorder and vascular injuries in streptozotocin (STZ)-induced diabetic rats through increasing plasma triglycerides and lipid peroxidation. Conversely, oral delivery of nCOF/Insulin ameliorated hemostatic disorders and restored the endothelial oxidant/antioxidant balance by reducing lipid peroxidation and enhancing the lipid profile. Our study pioneers the understanding of how STZ-induced diabetes disrupts bleeding time, induces a hypercoagulable state, and causes vascular damage through lipid peroxidation. Additionally, it provides the first evidence for the involvement of subcutaneous insulin treatment in exacerbating vascular and hemostasis disorders in type 1 diabetes (T1D). Introducing an innovative oral insulin delivery via the nCOF approach represents a potential paradigm shift in diabetes management and patient care and promises to improve treatment strategies for type 1 Diabetes.

cRGD-Peptide Modified Covalent Organic Frameworks for Precision Chemotherapy in Triple-Negative Breast Cancer.

This study presents the use of nanoscale covalent organic frameworks (nCOFs) conjugated with tumor-targeting peptides for the targeted therapy of triple-negative breast cancer (TNBC). While peptides have previously been used for targeted delivery, their conjugation with COFs represents an innovative approach in this field. In particular, we have developed alkyne-functionalized nCOFs chemically modified with cyclic RGD peptides (Alkyn-nCOF-cRGD). This configuration is designed to specifically target αvß3 integrins that are overexpressed in TNBC cells. These nCOFs exhibit excellent biocompatibility and are engineered to selectively disintegrate under acidic conditions, allowing for precise and localized drug release in tumor environment. Doxorubicin, a chemotherapeutic agent, has been encapsulated in these nCOFs with high loading efficiency. The therapeutic potential of Alkyn-nCOF-cRGD has been demonstrated in vitro and in vivo models. It shows significantly improved drug uptake and targeted cell death in TNBC, highlighting the efficacy of receptor-mediated endocytosis and pH-controlled drug release. This strategy leverages the unique properties of nCOFs with targeted drug delivery to achieve significant advances in personalized cancer therapy and set a new standard for precision chemotherapeutic delivery.

Separation of mercuric ions using 2-thienylbenzimidazole/cucurbit[7]uril/iron-oxide nanoparticles by pH control.

2-Thienylbenzimidazole (TBI)/cucurbit[7]uril (CB7) host-guest complex was used as a motif to significantly improve the turnover of γ-Fe3O4 magnetic nanoparticles for potential application in the separation of toxic mercuric ions in polluted water samples. The mechanism of restoring the original solid materials is based on applying the pH-controlled preferential binding of the CB7 host to the TBI guest. The analytical application of this concept has not been realized in the literature. The pH-controlled stimuli-responsive abilities were confirmed in aqueous solution by the three-order of magnitudes higher stability constant of the protonated TBIH+/CB7 complex (e.g., K = 4.8 × 108 M-1) when compared to neutral TBI/CB7 complex (e.g., K = 2.4 × 105 M-1), also manifested in an increase in pKa values by ~ 3.3 units in the ground state. The supramolecular interaction and adsorption on iron oxide nanoparticles (NPs) were also spectroscopically confirmed in the solid state. The excited-state lifetime values of TBI/CB7NPs increased upon lowering the pH values (e.g., from 0.6 to 1.3 ns) with a concomitant blue shift of ~ 25 nm because of polarity effects. The time-resolved photoluminescent behaviors of the final solids in the presence of CB7 ensured pH-driven reusable systems for capturing toxic mercuric ions. The study offers a unique approach for the controllable separation of mercury ions using an external magnet and in response to pH through preferential binding of the host to guest molecules on the top of magnetic surfaces.

Fluorescence turn on amine detection in a cationic covalent organic framework.

Ionic covalent organic frameworks (iCOFs) are new examples of porous materials and have shown great potential for various applications. When functionalized with suitable emission sites, guest uptake via the ionic moieties of iCOFs can cause a significant change in luminescence, making them excellent candidates for chemosensors. In here, we present a luminescence sensor in the form of an ionic covalent organic framework (TGH+•PD) composed of guanidinium and phenanthroline moieties for the detection of ammonia and primary aliphatic amines. TGH+•PD exhibits strong emission enhancement in the presence of selective primary amines due to the suppression of intramolecular charge transfer (ICT) with an ultra-low detection limit of 1.2 × 10‒7 M for ammonia. The presence of ionic moieties makes TGH+•PD highly dispersible in water, while deprotonation of the guanidinium moiety by amines restricts its ICT process and signals their presence by enhanced fluorescence emission. The presence of ordered pore walls introduces size selectivity among analyte molecules, and the iCOF has been successfully used to monitor meat products that release biogenic amine vapors upon decomposition due to improper storage.

A multimodal magnetic resonance imaging nanoplatform for cancer theranostics.

We describe an innovative multimodal system, which combines magnetic targeting of therapeutic agents with both magnetic resonance and fluorescence imaging into one system. This new magnetic nanoplatform consists of superparamagnetic γFe(2)O(3) nanoparticles, used clinically as an MRI contrast agent, conjugated to therapeutic molecules of the hydroxylmethylene bisphosphonate family (HMBPs): alendronate with an amine function as the terminal group. In vitro tests with breast cancer cells show that the γFe(2)O(3)@alendronate hybrid nanomaterial reduces cell viability and acts as a drug delivery system. We also investigated the anti-tumoural properties in vivo in nude mice xenografted with MDA-MB-231 tumours. We show that the presence of both γFe(2)O(3)@alendronate and a magnetic field significantly reduced the development of tumours. The amine functionalities can be used as precursor groups for the covalent coupling of peptides or monoclonal antibodies for specific biological targeting. The feasibility of this process was demonstrated by coupling rhodamine B, a fluorescence marker, to the γFe(2)O(3)@alendronate nanohybrid. The system showed fluorescent properties and high affinity for cells. Flow cytometry and fluorescence microscopy were used to study the kinetics of γFe(2)O(3)@alendronate uptake by cells. The magnetic and fluorescent nanoparticles are potential candidates for smart drug-delivery systems. Also, the superparamagnetic behaviour of such nanoparticles may be exploited as MRI contrast agents to improve therapeutic diagnostics.

Viologen-cucurbituril host/guest chemistry - redox control of dimerization versus inclusion.

Two calix[4]arene systems, C234+ and C244+ - where 2 corresponds to the number of viologen units and 3-4 corresponds to the number of carbon atoms connecting the viologen units to the macrocyclic core - have been synthesized and led to the formation of [3]pseudorotaxanes when combined with either CB[7] or CB[8]. The [3]pseudorotaxanes spontaneously dissociate upon reduction of the bipyridinium units as the result of intramolecular dimerization of the two face-to-face viologen radical cations. CB[7] and CB[8]-based [2]pseudorotaxanes containing monomeric viologen guest model compounds, MC32+ and MC4+, do not undergo decomplexation and dimerization following electrochemical reduction of their bipyridinium units.

In vivo oral insulin delivery via covalent organic frameworks.

With diabetes being the 7th leading cause of death worldwide, overcoming issues limiting the oral administration of insulin is of global significance. The development of imine-linked-covalent organic framework (nCOF) nanoparticles for oral insulin delivery to overcome these delivery barriers is herein reported. A gastro-resistant nCOF was prepared from layered nanosheets with insulin loaded between the nanosheet layers. The insulin-loaded nCOF exhibited insulin protection in digestive fluids in vitro as well as glucose-responsive release, and this hyperglycemia-induced release was confirmed in vivo in diabetic rats without noticeable toxic effects. This is strong evidence that nCOF-based oral insulin delivery systems could replace traditional subcutaneous injections easing insulin therapy.

Potent and selective in vitro and in vivo antiproliferative effects of metal-organic trefoil knots.

A set of metal-organic trefoil knots (M-TKs) generated by metal-templated self-assembly of a simple pair of chelating ligands were well tolerated in vitro by non-cancer cells but were significantly more potent than cisplatin in both human cancer cells--including those resistant to cisplatin--and in zebrafish embryos. In cultured cells, M-TKs generated reactive oxygen species that triggered apoptosis via the mitochondrial pathway without directly disrupting the cell-membrane or damaging nuclear DNA. The cytotoxicity and wide scope for structural variation of M-TKs indicate the potential of synthetic metal-organic knots as a new field of chemical space for pharmaceutical design and development.

Correction: Covalent organic nanosheets for bioimaging.

[This corrects the article DOI: 10.1039/C8SC02842G.].