Highly proliferative intestinal stem cells (ISCs) residing at the crypt base are key drivers of epithelial regeneration, playing critical role in promoting mucosal healing and sustaining long-term control of intestinal inflammation. However, most current approaches fail to access the crypt base and directly modulate the ISCs niche due to lack of sufficient tissue penetrability and deformability. To address this challenge, we develop an orally administered regenerative coacervate (ReCOAT) featuring a stress-relaxing fluid property, benefiting from the dynamic internal interaction network formed between robust titanium-based metal-organic frameworks (Ti-MOFs) nanoparticles and 8-arm poly(ethylene glycol) (PEG). This mechanical feature enables ReCOAT to conform to recessed crypts and damaged mucosal folds, intimately engages the ISCs niche and locally normalizes its biophysical homeostasis. ReCOAT thus promotes ISCs proliferation and differentiation by providing a soft, stress-relaxing matrix in which ISCs-generated traction forces are initially transmitted but then dissipated over time, facilitating epithelia restoration and inflammation prevention. In both acute and chronic inflammatory bowel disease (IBD) models, orally delivered ReCOAT treatment conformally covers inflamed colonic mucosa, accelerating epithelial restoration and attenuating colonic inflammation, and ultimately suppressing disease progression and recurrence. These findings establish a biomechanically targeted, orally deliverable strategy for in situ normalization of the ISCs niche, offering a viable strategy for durable mucosal healing in IBD.

Cardiovascular disease (CVD) is one of the most critical diseases which is the predominant cause of death in the world. Early screening and diagnosis of the disease and effective treatment after diagnosis play an important role in the patient's recovery. Metal-organic frameworks (MOFs), a kind of hybrid ordered micro or meso-porous materials, constructed by metal nodes or clusters with organic ligands, due to their special features like high porosity and specific surface area, open metal sites, or ligand tunability, are widely used in various areas including gas storage, catalysis, sensors, biomedicine. Recently, advances in MOFs are bringing new developments and opportunities for the healthcare industry including the theranostic of CVD. In this review, the applications of MOFs are illustrated in the diagnosis and therapy of CVD, including biomarker detection, imaging, drug delivery systems, therapeutic gas delivery platforms, and nanomedicine. Also, the toxicity and biocompatibility of MOFs are discussed. By providing a comprehensive summary of the role played by MOFs in the diagnosis and treatment of CVDs, it is hoped to promote the future applications of MOFs in disease theranostics, especially in CVDs.

Brachytherapy, or internal radiation therapy, is a highly effective treatment option for localized tumors. Herein, injectable and biodegradable metal-organic frameworks (MOFs) were engineered to deliver the therapeutic radioisotope yttrium-90 (90Y). Particles of bimetallic MIL-100(Fe,Y) and Y-BTC, doped with 90Y and 88Y, were synthesized in a single step and retained radioyttrium in various buffer solutions. Tumor injectability and radioisotope retention were evaluated using tumor-bearing mice. In vivo analysis and calculations showed that radiolabeled MIL-100(Fe,Y) emitted more than 38% of its radioactivity, while Y-BTC emitted greater than 75% of its radioactivity, for 7 days at the tumor site upon intratumoral injection, without significant yttrium accumulation in off-target tissues. The anticancer effects of MIL-100(Fe,Y,90Y) and 90Y,Y-BTC particles were assessed using 3D multicellular tumor spheroids and a tumor-bearing mouse model, respectively. 90Y-doped MIL-100(Fe,Y) particles penetrated A549 tumor spheroids and caused superior cytotoxic effects compared to non-radioactive particles or 90YCl3, added at the same dose. Brachytherapy with 90Y-doped Y-BTC MOFs induced inhibition of B16F1 melanoma tumor growth and resulted in an increased median survival of 8.5 days compared to 4.5 days in untreated mice. This study shows the feasibility of preparing radioactive 90Y-containing biodegradable non-toxic MOF particles that are advantageous for low-dose rate internal radiotherapy.

Over the past two decades, iron-based metal-organic frameworks (Fe-MOFs) have attracted significant research interest in biomedicine due to their low toxicity, tunable degradability, substantial drug loading capacity, versatile structures, and multimodal functionalities. Despite their great potential, the transition of Fe-MOFs-based composites from laboratory research to clinical products remains challenging. This review evaluates the key properties that distinguish Fe-MOFs from other MOFs and highlights recent advances in synthesis routes, surface engineering, and shaping technologies. In particular, it focuses on their applications in biosensing, antimicrobial, and anticancer therapies. In addition, the review emphasizes the need to develop scalable, environmentally friendly, and cost-effective production methods for additional Fe-MOFs to meet the specific requirements of various biomedical applications. Despite the ability of Fe-MOFs-based composites to combine therapies, significant hurdles still remain, including the need for a deeper understanding of their therapeutic mechanisms and potential risks of resistance and overdose. Systematically addressing these challenges could significantly enhance the prospects of Fe-MOFs in biomedicine and potentially facilitate their integration into mainstream clinical practice.

Electrospray ionization is widely used to generate vapor phase ions for analysis by mass spectrometry in proteomics research. However, only a small fraction of the analyte enters the mass spectrometer due to losses that are fundamentally linked to the use of a background gas to stimulate the generation of ions from electrosprayed droplets. Here we report a nanopore ion source that delivers ions directly into high vacuum from aqueous solutions. The ion source comprises a pulled quartz pipette with a sub-100 nm opening. Ions escape an electrified meniscus by ion evaporation and travel along collisionless trajectories to the ion detector. We measure mass spectra of 16 different amino acid ions, post-translationally modified variants of glutathione, and the peptide angiotensin II, showing that these analytes can be emitted as desolvated ions. The emitted current is composed of ions rather than charged droplets, and more than 90% of the current can be recovered in a distant collector. Electrospray ionization loses most ions upon transfer into high vacuum in a mass spectrometer. Here, the authors present a nanopore ion source that emits ions directly into vacuum from aqueous solutions, achieving an ion transmission efficiency of over 90%.

Phototherapy is a low-risk alternative to traditional antibiotics against drug-resistant bacterial infections. However, optimizing phototherapy agents, refining treatment conditions, and addressing misuse of agents, remain a formidable challenge. This study introduces a novel concept leveraging the unique customizability of metal-organic frameworks (MOFs) to house size-matched dye molecules in “single rooms”. The mesoporous iron(III) carboxylate nanoMOF, MIL-100(Fe), and the hydrophobic heptamethine cyanine photothermal dye (Cy7), IR775, are selected as model systems. Their combination is predicted to minimize dye-dye interactions, leading to exceptional photostability and efficient light-to-heat conversion. Furthermore, MIL-100(Fe) preserves the antimicrobial nature of hydrophobic IR775, enabling it to disrupt bacterial cell envelopes. Through electrospinning, MIL-100(Fe)@IR775 nanoparticles are shaped into a gelatin-based film dressing for the treatment of skin wounds infected by Methicillin-resistant Staphylococcus aureus (MRSA). Activation of the dressing requires only a portable near-infrared light-emitting diode (NIR LED) and induces both low-dose photodynamic therapy (LPDT) and mild-temperature photothermal therapy (MPTT). Combined with the antimicrobial properties of IR775 and ferroptosis-like lipid peroxidation induced by MIL-100(Fe), the photoactive dressing eradicates MRSA and the healing is as quick as the uninfected wounds. This safe, cost-effective, and multifunctional therapeutic wound dressing offers a promising solution to overcome the current bottleneck in phototherapy.

Brachytherapy, or intratumoral radiation therapy, is a highly effective treatment option for localized tumors. Herein, we engineered injectable and biodegradable metal-organic frameworks (MOFs) to deliver the therapeutic radioisotope yttrium-90 (90Y). Particles of bimetallic MIL-100(Fe,Y) and Y-BTC, doped with 90Y and 88Y, were synthesized in a single step and retained radioyttrium in various buffer solutions. Tumor injectability and radioisotope retention were evaluated using tumor-bearing mice. In vivo analysis and calculations showed that radiolabeled MIL-100(Fe,Y) emitted more than 38% of its radioactivity, while Y-BTC emitted greater than 75% of its radioactivity, through 7 days at the tumor site upon intratumoral injection, without significant yttrium accumulation in off-target tissues. The anticancer effects of MIL-100(Fe,Y,90Y) and 90Y,Y-BTC particles were assessed using 3D multicellular tumor spheroids and a tumor-bearing mouse model, respectively. 90Y-doped MIL-100(Fe,Y) particles penetrated A549 tumor spheroids and caused superior cytotoxic effects compared to non-radioactive particles or 90YCl3, added at the same dose. Brachytherapy with 90Y-doped Y-BTC MOFs induced inhibition of B16F1 melanoma tumor growth and resulted in an increased median survival of 8.5 days compared to 4.5 days in untreated mice. This study exhibits the feasibility to prepare radioactive 90Y-containing biodegradable, non-toxic MOF particles that are advantageous for low-dose rate internal radiotherapy. ### Competing Interest Statement The authors have declared no competing interest.

The use of single track-etched nanopores to distinguish molecules is limited by the difficulty in comparing independent experiments. This is mainly because the properties (size, surface state) among various equivalent nanopores are not strictly identical. In this work, we propose a way to discriminate different sized gold nanoparticles coated with PEG from 38 to 90 nm using bullet-like shape nanopores with tip diameters of 100 and 130 +/- 30 nm, functionalized with polyethylene glycol (PEG) chains of different lengths (5 and 20 kDa). We show that the two classical parameters of current perturbations (the relative blockade amplitude and the dwell time) caused by the interaction of the nanoparticles with the nanopore allow the discrimination of the nanoparticles using each nanopore independently. Indeed, both the nanopore diameter and the PEG length influence the current blockade parameter, showing that it is possible to distinguish nanoparticles from independent experiments despite the inherent variability of the track-etched nanopores.

A new process, PMOFSA, is described here, that opens the way for the one-pot straightforward and versatile manufacture of polymer-MOF nanoparticles in water. It can be expected that this study will not only expand the scope of in situ preparation of polymer-MOF nano-objects but also inspire researchers in the field to prepare a new generation of polymer-MOF hybrid materials.

Nanoparticles of biocompatible iron carboxylate metal-organic frameworks (MOFs) or nanoMOFs are of great interest for biomedicine, in particular, for controlled drug release. However, little is known about the impact of their synthesis protocols on their defect content and the possible consequences in terms of physicochemical features and cytotoxicity. Here, we report for the first time how the defect content of the benchmark mesoporous iron trimesate MIL-100-(Fe) (MIL stands for Materials of Institut Lavoisier) nanoparticles, with similar sizes but obtained from three different green synthesis routes, has a significant impact not only on their intrinsic porosity, stability in body fluids, drug loading capacity, and release but also shows a critical difference of in vitro toxicity and inflammatory response depending on the type of cell lines.

Metal-organic framework nanoparticles (nanoMOFs) are a promising class of hybrid nanomaterials for biomedical applications. Some of them, including biodegradable porous iron carboxylates are proposed for encapsulation and delivery of antibiotics. Due to the high drug loading capacity and fast internalization kinetics nanoMOFs are more beneficial for the treatment of intracellular bacterial infections compared to free antibacterial drugs, which poorly accumulate inside the cells because of the inability to cross membrane barriers or have low intracellular retention. However, nanoparticle internalization does not ensure their accumulation in the cell compartment that shelters a pathogen. This study shows the availability of MIL-100(Fe) MOF nanoparticles to co-localize with Chlamydia trachomatis , an obligate intracellular bacterium, in the infected RAW264.7 macrophages. Furthermore, nanoMOFs loaded with photosensitizer methylene blue (MB) exhibit complete photodynamic inactivation of Chlamydia trachomatis growth. Simultaneous infection and treatment of RAW264.7 cells with empty nanoMOFs resulted in a 3-fold decrease in bacterial load that indicates an intrinsic anti-chlamydial effect of this iron-containing nanomaterial. Thus, our findings suggest the use of iron-based nanoMOFs as a promising drug delivery platform, which contributes to antibacterial effect, for the treatment of chlamydial infections. ### Competing Interest Statement The authors have declared no competing interest.

Metal-organic framework nanoparticles (nanoMOFs) are promising nanomaterials for biomedical applications. Some of them, including biodegradable porous iron carboxylates are proposed for encapsulation and delivery of antibiotics. Due to the high drug loading capacity and fast internalization kinetics, nanoMOFs are more beneficial for the treatment of intracellular bacterial infections compared to free antibacterial drugs, which poorly accumulate inside the cells because of the inability to cross membrane barriers or have low intracellular retention. However, nanoparticle internalization does not ensure their accumulation in the cell compartment that shelters a pathogen. This study shows the availability of MIL-100(Fe)-based MOF nanoparticles to co-localize with Chlamydia trachomatis, an obligate intracellular bacterium, in the infected RAW264.7 macrophages. Furthermore, nanoMOFs loaded with photosensitizer methylene blue (MB) exhibit complete photodynamic inactivation of C. trachomatis growth. Simultaneous infection and treatment of RAW264.7 cells with empty nanoMOFs resulted in a bacterial load reduction from 100 to 36% that indicates an intrinsic anti-chlamydial effect of this iron-containing nanomaterial. Thus, our findings suggest the use of iron-based nanoMOFs as a promising drug delivery platform, which contributes to antibacterial effect, for the treatment of chlamydial infections.

In this work, we aim to capture, detect and analysis at single molecule level Aβ42 aggregates. To this end, two strategies of track-etched nanopore membranes functionalization were investigated. The first one uses an aptamer and requires only three steps, whereas the second strategy uses Lecanemab antibodies and requires six steps. Out of the two presented strategies, the second one was found to be the most suitable to detect Aβ42 aggregates using a quick current-voltage readout. The resulting single nanopore was then upscale to multipore membranes to capture the Aβ42 aggregates before analysis through them through a single-molecule approach. By comparing the species present in the retentate and filtrate, we confirmed the membrane's affinity for the larger Aβ42 aggregates present in the sample. We found that chromatographic membranes combined with an ionic diode for binary on/off readout are powerful tools for detecting rare biomarkers before single molecule analysis.

Metal-organic frameworks (MOFs) are a highly versatile class of ordered porous materials, which hold great promise for different biomedical applications, including antibacterial therapy. In light of the antibacterial effects, these nanomaterials can be attractive for several reasons. First, MOFs exhibit a high loading capacity for numerous antibacterial drugs, including antibiotics, photosensitizers, and/or photothermal molecules. The inherent micro- or meso-porosity of MOF structures enables their use as nanocarriers for simultaneous encapsulation of multiple drugs resulting in a combined therapeutic effect. In addition to being encapsulated into an MOF’s pores, antibacterial agents can sometimes be directly incorporated into an MOF skeleton as organic linkers. Next, MOFs contain coordinated metal ions in their structure. Incorporation of Fe2/3+, Cu2+, Zn2+, Co2+, and Ag+ can significantly increase the innate cytotoxicity of these materials for bacteria and cause a synergistic effect. Finally, abundance of functional groups enables modifying the external surface of MOF particles with stealth coating and ligand moieties for improved drug delivery. To date, there are a number of MOF-based nanomedicines available for the treatment of bacterial infections. This review is focused on biomedical consideration of MOF nano-formulations designed for the therapy of intracellular infections such as Staphylococcus aureus, Mycobacterium tuberculosis, and Chlamydia trachomatis. Increasing knowledge about the ability of MOF nanoparticles to accumulate in a pathogen intracellular niche in the host cells provides an excellent opportunity to use MOF-based nanomedicines for the eradication of persistent infections. Here, we discuss advantages and current limitations of MOFs, their clinical significance, and their prospects for the treatment of the mentioned infections.

Multidrug-resistant microbes have become a serious problem worldwide due to the misuse of antibacterial agents. Photodynamic therapy (PDT) and photothermal therapy (PTT) have been considered promising alternative approaches to replace or combine traditional antimicrobial treatment [1]. Moreover, photoacoustic (PA)-guided PTT is motivating the development of precise and effective treatment. However, many photosensitizers show low efficiency of reactive oxygen species (ROS) generation or light heat conversion, low bioavailability, photostability, and high cytotoxicity. Metal-organic frameworks (MOFs) are a group of crystalline coordinating materials based on cations connected through organic linkers ended by complexing groups, which show high potential in the development of new antimicrobial agents, due to their unique properties such as ultra-high surface area, tuned but consistent pore sizes, strong thermal stability, and easy synthesis. We selected iron-based MOF MIL-100(Fe) due to its great biocompatibility and large drug storage space.

ABSTRACT Metal-organic framework nanoparticles (nanoMOFs) are a promising class of hybrid nanomaterials for biomedical applications. Some of them, including biodegradable porous iron carboxylates are proposed for encapsulation and delivery of antibiotics. Due to the high drug loading capacity and fast internalization kinetics nanoMOFs are more beneficial for the treatment of intracellular bacterial infections compared to free antibacterial drugs, which poorly accumulate inside the cells because of the inability to cross membrane barriers or have low intracellular retention. However, nanoparticle internalization does not ensure their accumulation in the cell compartment that shelters a pathogen. This study shows the availability of MIL-100(Fe) MOF nanoparticles to co-localize with Chlamydia trachomatis , an obligate intracellular bacterium, in the infected RAW264.7 macrophages. Furthermore, nanoMOFs loaded with photosensitizer methylene blue (MB) exhibit complete photodynamic inactivation of Chlamydia trachomatis growth. Simultaneous infection and treatment of RAW264.7 cells with empty nanoMOFs resulted in a 3-fold decrease in bacterial load that indicates an intrinsic anti-chlamydial effect of this iron-containing nanomaterial. Thus, our findings suggest the use of iron-based nanoMOFs as a promising drug delivery platform, which contributes to antibacterial effect, for the treatment of chlamydial infections.

The need for antibody proteins is growing for both diagnosis and therapy. In this work, we combine two strategies based on single nanopore sensing and multipore membrane to separate, detect and identify antibodies. This proof of concept was done for the anti-CD44. In a first step, a single nanopore with a bullet shape were designed using track-etching of polymer film and functionalized, with a PEG spacer and CD44 antigen. The detection of anti-CD44 was evidenced by an inversion of the current rectification. After demonstrating the ability to specifically detect the antiCD44 in a single nanopore, a multipore membrane with cylindrical nanopore was designed following the same protocol and used to elute a solution of anti-CD44.In a second step, the elution product was analysed using a single SiN nanopore showing that the anti-CD44 and CD44 antigen are extracted from the membrane. The analysis of the amplitude of the current blockade shows that the complex is dissociated.

We report a nanopore ion source for mass spectrometry that delivers ions directly into high vacuum from aqueous solutions. The ion source comprises a pulled quartz capillary with a sub-100~nm opening. Ions escape an electrified meniscus between the liquid and high vacuum by ion evaporation and travel along collisionless trajectories to the ion detector. We measure mass spectra of 16 different amino acid ions as well as post-translationally modified variants of glutathione in unsolvated states using the nanopore ion source. The emitted current is composed of ions rather than charged droplets, and more than 90% of the current can be recovered in a distant collector. The nanopore ion source could enable more sensitive proteomic analyses. It circumvents the sample loss mechanisms inherent to conventional electrospray ionization (ESI), where charged droplets are sprayed into a background gas that scatters ions and degrades their transmission.

Several neurodegenerative diseases have been linked to proteins or peptides that are prone to aggregate in different brain regions. Aggregation of amyloid-β (Aβ) peptides is recognized as the main cause of Alzheimer's disease (AD) progression, leading to the formation of toxic Aβ oligomers and amyloid fibrils. The molecular mechanism of Aβ aggregation is complex and still not fully understood. Nanopore technology provides a new way to obtain kinetic and morphological aspects of Aβ aggregation at a single-molecule scale without labeling by detecting the electrochemical signal of the peptides when they pass through the hole. Here, we investigate the influence of nanoscale geometry (conical and bullet-like shape) of a track-etched nanopore pore and the effect of molecular crowding (polyethylene glycol-functionalized pores) on Aβ fibril sensing and analysis. Various Aβ fibril samples that differed by their length were produced by sonication of fibrils obtained in the presence of epigallocatechin gallate. The conical nanopore functionalized with polyethylene glycol (PEG) 5 kDa is suitable for discrimination of the fibril size from relative current blockade. The bullet-like-shaped nanopore enhances the amplitude of the current and increases the dwell time, allowing us to well discern the fibrils. Finally, the nanopore crowded with PEG 20 kDa enhances the relative current blockade and increases the dwell time; however, the discrimination is not improved compared to the "bullet-shaped" nanopore.