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Atherosclerosis, a major global health concern with high morbidity and mortality rates, involves complex interactions of chronic inflammation, oxidative stress, and proteolytic enzymes. Conventional imaging methods struggle to capture the dynamic biochemical processes in atherosclerotic plaques. Here, we introduce a novel unimolecular photoacoustic probe (UMAPP) designed with specific binding sites for neutrophil elastase (NE) and the redox pair O 2 ⋅ - /GSH, enabling real-time monitoring of oxidative stress and activated neutrophils in plaques. UMAPP, comprising a boron-dipyrromethene (BODIPY) core linked to a hydrophilic NE-cleavable tetrapeptide and dual oxidative stress-responsive catechol moieties, facilitates NE-mediated modulation of photoinduced electron transfer impacting photoacoustic intensity at 685 nm (PA 685 ). Furthermore, oxidation and reduction of catechol groups by O 2 ⋅ - and GSH induce reversible, ratiometric changes in the photoacoustic spectrum (PA 745 /PA 685 ratio). Initial UMAPP applications successfully distinguished atherosclerotic and healthy mice, evaluated pneumonia's effect on plaque composition and verified the probe's effectiveness in drug-treatment studies by detecting molecular alterations before visible histopathological changes. The integrated molecular imaging capabilities of UMAPP offer promising advancements in atherosclerosis diagnosis and management, enabling early and accurate identification of vulnerable plaques., (© 2024 Wiley-VCH GmbH.)

Drug resistance in B cell leukemia is characterized by the coexpression of CXCR5 and CXCR3 chemokine receptors, making it a valuable biomarker for patient stratification. Herein, we report a novel platform of activatable chemokines to selectively image drug-resistant leukemic B cells for the first time. The C-terminal derivatization of the human chemokines CXCL13 and CXCL10 with bioorthogonal tetrazine-BODIPY and BCN groups retained binding and internalization via their cognate CXCR5 and CXCR3 receptors and enabled rapid fluorescence labeling of CXCR5+ CXCR3+ resistant B cells─but not drug-susceptible leukemic cells─via intracellular chemokine ligation. This modular chemical approach offers a versatile strategy for real-time immunophenotyping of cell populations with distinct chemokine profiles and will accelerate the design of new precision medicine tools to advance personalized therapies in blood tumors.

Tumor microenvironment-activatable photosensitizers have gained significant attention for cancer theranostics. Considering the hypoxic environment of solid tumors, activatable phototheranostic agents with type I PDT are desired to obtain improved cancer treatment efficiency. Herein, we report a simple, effective and multifunctional Bodipy photosensitizer for tumor imaging and type I/II photodynamic therapy. The photosensitizer featuring a methylphenylboronic acid pinacol ester group at the meso -position of Bodipy specifically responds to tumor-abundant H 2 O 2 . Its photophysical properties were characterized using steady-state and time-resolved transient optical spectroscopies. The fluorescence ( Φ F = 0.09%) and singlet oxygen efficacy ( Φ Δ = 10.2%) of the Bodipy units were suppressed in the caged dyads but significantly enhanced ( Φ F = 0.72%, Φ Δ = 20.3%) upon H 2 O 2 activation. Fluorescence emission spectroscopy and continuous wave electron paramagnetic resonance (EPR) spectroscopy confirmed that the Bodipy photosensitizer generates reactive oxygen species (ROS) via both electron transfer-mediated type I and energy transfer-mediated type II mechanisms. In vitro experiments demonstrated rapid internalization into tumor cells, enhanced brightness stimulated by tumor microenvironments, and tumor cell death (phototoxicity, IC 50 = 0.5 μM). In vivo fluorescence imaging indicated preferential accumulation of this Bodipy photosensitizer in tumor sites, followed by decaging by tumor-abundant H 2 O 2 , further elevating the signal-to-background ratio (SBR) of imaging. Besides outstanding performance in tumor imaging, a prominent inhibition of tumor growth was observed. Given its simple molecular skeleton, this Bodipy photosensitizer is a competitive candidate for cancer theranostics.

Thiophenol (PhSH) is an important industrial intermediate but displays significant toxicity towards environmental and biological systems. Here, we introduce a supramolecular system based on β-cyclodextrin (β-CD) and boron dipyrromethene (BODIPY) as a ratiometric fluorescence probe to discriminate PhSH in environmental water samples, cells, and in vivo. In aqueous solutions, BODIPY shows extremely weak fluorescence intensity due to its aggregation into nanometer-sized clusters, which prevents its interaction with thiols. However, within a β-CD environment, it can selectively and sensitively detect PhSH. Also, the stability of the probe was significantly improved. The mechanism studies based on stoichiometry, NMR spectroscopy, and theoretical calculation revealed distinct intermolecular interactions between β-CD and BODIPY, including host-guest interactions and hydrogen bonds. Low limit of detection (10.7 nM) and rapid response time (5 min) have been achieved, and the practicality of the supramolecular system (BODIPY@β-CD) has been verified by actual sample analysis. Furthermore, the first hydrogel-based sensing system for portable PhSH detection has been developed, facilitating rapid and on-site colorimetric visualization across both liquid and gas phases. Most importantly, using a low amount of the probe, early stages of low-dose exposure to PhSH can be visualized in living cells and zebrafish. Therefore, BODIPY@β-CD is a robust new monitoring tool for the detection of PhSH in various scenarios, indicating the promising application value of the host-guest supramolecular probe in detecting highly toxic substances., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

In living systems, protein assemblies have essential functions, serving as structural supports, transport highways for molecular cargo, and containers of genetic material. The construction of protein assemblies, which involves control over space and time, remains a significant challenge in biotechnology. Here, we show that anionic boron clusters, 3,3'-commo-bis[closo-1,2-dicarba-3-cobaltadodecaborane] (COSAN - ), and halogenated closo-dodecarboranes (B 12 X 12 2- , X=H, Cl, or I), described as super-chaotropic nano-ions, induce the formation of 2D assemblies of model proteins, myoglobin, carbonic anhydrase, and trypsin inhibitor. We found that the nano-ion concentration reversibly controls the size of the protein assemblies. Furthermore, the secondary structures of the proteins are only slightly affected by assembly formation. For myoglobin, the formation of these assemblies even prevents temperature denaturation, highlighting a preservation effect of nano-ions. Our study reveals that inorganic boron-based nano-ions act as a reversible molecular glue for proteins, providing a potential starting point for the further development of controlled protein assemblies., (© 2024 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Boron neutron capture therapy (BNCT) is one of the most promising modalities for cancer treatment due to its minimal invasiveness. Although two types of boron agents are clinically used, several issues persist in their delivery, including poor water solubility, instability in aqueous media, selectivity toward cancer cells, accumulation in cancer cells, retention time in tumor tissue, and efficiency in achieving the boron neutron capture reaction. Addressing these challenges, numerous groups have explored various boron agents to enhance the therapeutic benefits of BNCT. This review summarizes delivery platforms based on natural products for BNCT., (© 2024 Wiley-VCH GmbH.)

An innovative organic small molecule with a D-A structure was synthesized by connecting triphenylamine to BODIPY via a thiophene bridge. Triphenylamine and thiophene units ingeniously modulate the balance between steric hindrance and π-π interactions around the flat aza-BODIPY core. The molecule exhibits near-infrared fluorescence absorption and emits at roughly 1100 nm, featuring a significant Stokes shift. Both the molecule and its nanoparticles demonstrate high stability and achieve a remarkable 35 % photothermal conversion efficiency when conjugated with the P(OEGMA) 20 -P(Asp) 14 copolymer. In vitro assessments show low dark toxicity and outstanding biocompatibility. Moreover, in vivo studies and photothermal therapy in mice indicate substantial tumor shrinkage and reduced recurrence, confirming its potential in cancer treatment. These results highlight the promise of this organic molecule and its nanoparticles for NIR-II imaging-guided photothermal therapy, introducing a novel approach to phototheranostic applications for cancer management., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Human urine phosphorus (existing in the form of phosphate) is a biomarker for the diagnosis of several diseases such as kidney disease, hyperthyroidism, and rickets. Therefore, the selective detection of phosphate in urine samples is crucial in the field of clinical diagnosis. Herein, we reported the phosphatase-like catalytic activity of few-layered h-BNNS for the first time. As the phosphatase-like activity of few-layered h-BNNS could be effectively inhibited by phosphate, a selective fluorescent method for the detection of phosphate was proposed. The linear range for phosphate detection is 0.5-10 µM with a detection limit of 0.33 µM. The fluorescent method was then explored for the detection of human urine phosphorus in real samples. The results obtained by the proposed method were consistent with those of the traditional method, indicating that the present method has potential application for urine phosphorus detection in clinical disease diagnosis., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

Nanomaterial-cellular membrane interaction is crucial for the cytotoxicity of such materials in theoretical investigations. However, previous research often used cellular membrane models with one or few lipid types, which deviates significantly from realistic membrane compositions. Here, employing molecular dynamics (MD) simulations, we investigate the impact of a typical nanomaterial, boron nitride (BN), on a cellular membrane model based on the realistic small intestinal epithelial cell (SIEC) membrane. This membrane contains a complex composition, including abundant glycolipids. Our MD simulations reveal that BN nanosheet can partially insert into the SIEC membrane, maintaining a stable binding conformation without causing obvious structural changes. Dynamic analyses suggest that van der Waals (vdW) interactions drive the binding process between BN and the SIEC membrane. Further simulation of the interaction between BN nanosheet and deglycosylated SIEC membrane confirms that BN nanosheet cause significant structural damage to deglycosylated SIEC membranes, completely inserting into the membrane, extracting lipids, and burying some lipid hydrophilic heads within the membrane interior. Quantitative analyses of mean squared displacements (MSD) of membranes, membrane thicknesses, area per lipid, and order parameters indicate that BN nanosheet causes more substantial damage to deglycosylated SIEC membrane than to intact SIEC membrane. This comparison suggests the molecular mechanism involved in mitigating BN invasion by SIEC membrane that the polysaccharide heads of glycolipids in the SIEC membrane form a significant steric hindrance on membrane surface, not only hindering the insertion of BN, but also resisting the lipid extraction by BN. Free energy calculations further support this conclusion. Overall, our MD simulations not only shed new light into the reduced impact of BN nanosheet on the realistic SIEC membrane but also highlight the importance of glycolipids in protecting cell membranes from nanomaterial invasion, contributing to a deeper understanding of nanomaterial-realistic cell membrane interactions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Electron acceptor possessing strong electron-withdrawing ability and exceptional stability is crucial for developing donor-acceptor-donor (D-A-D) structured aggregation-induced emission luminogens (AIEgens) with second near-infrared (NIR-II) emission. Although 6,7-diphenyl-[1,2,5] thiadiazolo [3,4- g ] quinoxaline (PTQ) and benzobisthiadiazole (BBT) are widely employed as NIR-II building blocks, they still suffer from limited electron-withdrawing capacity or inadequate chemo-stability under alkaline conditions. Herein, a boron difluoride formazanate (BFF) acceptor is utilized to construct NIR-II AIEgen, which exhibits a better overall performance in terms of NIR-II emission and chemo-stability compared to the PTQ- and BBT-derived fluorophores. With finely tuned intramolecular motions and strong D-A interaction strength, TPE-BFF simultaneously exhibits high molar extinction coefficient ( ε= 4.31 × 10 4 M -1 cm -1 ), strong NIR-II emission (Φ = 0.49%) and photothermal effect (η = 58.5%), as well as high stability. Thanks to these merits, the thermosensitive nanoparticles constructed by integrating TPE-BFF and the antiglycolytic agent 2-deoxy-d-glucose (2DG) are successfully utilized for imaging-guided photothermal antitumor lung metastasis by regulating glycolysis and reducing ATP-dependent heat shock proteins. Combining experimental results and theoretical calculations, BFF proves to be an outstanding electron acceptor for the design of versatile NIR-II AIEgens. Overall, this study offers a promising alternative for developing multifunctional NIR-II AIEgens in biomedical applications.

The benzoxaborinine scaffold, a homologue of benzoxaborole with an additional carbon atom in the boracycle, shows significant potential in developing new therapeutic agents. This study reports the synthesis, inhibition assays against four human carbonic anhydrase (hCA, EC 4.2.1.1) isoforms, and anti-melanoma evaluation of 7-aryl(thio)ureido-substituted benzoxaborinines. Some derivatives, particularly compound 11 , exhibited potent inhibitory activity (below 65 nM) against hCA IX and XII and stronger antiproliferative effects than SLC-0111 on human melanoma cells under hypoxia. Crystallographic studies of benzoxaborinine 3 adducts with hCA I and II demonstrated the binding mode of this chemotype, revealing that although both benzoxaborinine 3 and benzoxaborole 10 share a similar zinc-binding mode, the expanded ring in benzoxaborinine led to a different orientation within the active site. These findings suggest that benzoxaborinines hold promise for designing novel carbonic anhydrase inhibitors.

Organoborons have recently received much attention, while a biocatalytic platform for the synthesis of chiral organoborons is limited only to Rma cytochrome c . In this study, we exploited the other heme protein, neuroglobin (Ngb), and engineered a quadruple mutant, A15C/H64G/V68F/F28M Ngb, by redesigning the heme active site using the structural information on A15C Ngb and molecular docking studies. The enzyme was shown to be efficient in catalyzing carbene transfer B-H insertion reactions between pyridine/quinoline boranes and benzyl 2-diazopropanoates and their derivatives (29 examples). The designed cavity in the heme distal site favors the binding of large volume substrates such as those containing a quinoline, naphthyl, or biphenyl group. As further determined by the X-ray crystallography of 6c , the chiral products are in the R -configuration, with up to 98:2 e.r. Furthermore, both the whole cell and cell lysate containing the enzyme are reactive toward the B-H insertion reactions. This study presents a convenient biocatalytic platform that may be generally applicable for the synthesis of functional chiral organoborons.

Tracking carboxylesterases (CESs) through noninvasive and dynamic imaging is of great significance for diagnosing and treating CES-related metabolic diseases. Herein, three BODIPY-based fluorescent probes with a pyridine unit quaternarized via an acetoxybenzyl group were designed and synthesized to detect CESs based on the photoinduced electron transfer process. Notably, among these probes, BDPN2-CES exhibited a remarkable 182-fold fluorescence enhancement for CESs within 10 min. Moreover, BDPN2-CES successfully enabled real-time imaging of endogenous CES variations in living cells. Using BDPN2-CES, a visual high-throughput screening method for CES inhibitors was established, culminating in the discovery of an efficient inhibitor, WZU-13, sourced from a chemical library. These findings suggest that BDPN2-CES could provide a new avenue for diagnosing CES-related diseases, and WZU-13 emerges as a promising therapeutic candidate for CES-overexpression pathological processes.

With the innovation of modern electronics, heat dissipation in the devices faces several problems. In our work, boron nitride (BN) with good thermal conductivity (TC) was successfully fabricated by constructing the BN along the axial direction and the surface-grafted BN hybrid composite fibers via the wet-spinning and hot-pressing method. The unique inter-outer and inter-interconnected hybrid structure of composite fibers exhibited 176.47% thermal conductivity enhancement (TCE), which exhibits good TC, mechanical resistance, and chemical resistance. In addition, depending on the special structure of the composite fibers, it provides a new strategy for fabricating thermal interface materials in the electronic device.

The development of new and improved mitochondria-targeting photosensitisers (PSs) for photodynamic therapy (PDT) remains highly desirable, due to the critical role the mitochondria play in maintaining healthy cellular function. Here, we report the design, synthesis, photophysical properties and biological characterisation of a series of di-iodinated BODIPY-based PSs, BODIPY-Mito-I-n, for mitochondria-targeted PDT applications. Six BODIPY-Mito-I-n analogues were synthesised in good yields, with fast reaction times of between 30 and 60 min under mild conditions. The di-iodination of the BODIPY scaffold enabled highly efficient population of the triplet state, leading to high singlet oxygen ( 1 O 2 ) photosensitisation efficiencies ( Φ Δ = 0.55-0.65). All BODIPY-Mito-I-n compounds exhibited very high photocytotoxic activity towards HeLa cells, with IC 50,light values of between 1.30 and 6.93 nM, due to photoinduced 1 O 2 generation. Notably, the poly(ethylene glycol) (PEG)-modified BODIPY-Mito-I-6 showed remarkably lower dark cytotoxicity (IC 50,dark = 6.68-7.25 μM) than the non-PEGylated analogues BODIPY-Mito-I-1 to BODIPY-Mito-I-5 (IC 50,dark = 0.58-1.09 μM), resulting in photocytotoxicity indices up to 2120. Mechanistic studies revealed that BODIPY-Mito-I-6 induced reactive oxygen species overproduction and mitochondrial dysfunction in cells upon irradiation, leading to significant cell death through a combination of apoptosis and necrosis. It is anticipated that our design will contribute to the development of more effective mitochondria-targeting PSs for cancer therapy.

Context: By delivering the drug to the intended cell location, the use of nanomaterials in the drug delivery system may influence how the patient receives the medication and may assist in mitigating severe side effects. Density functional theory was used to assess the use of boron carbon nitride nanocages (BNCNCs), boron nitride (BNNSs), and boron carbon nitride nanosheets (BNCNSs) as melphalan (Mln) drug carriers in both the gaseous and fluid phases. We systematically examined the dipole moment, density of states, frontier molecular orbital, and optimal adsorption energy to understand the targeted drug delivery potential of these nanostructures. Adsorption energy analysis revealed that in both gas and water media, Mln drug adsorption takes place spontaneously on all the conjugated structures. The occurrence of adsorption energy as physisorbed energy suggests that the process is reversible, and desorption can take place with a much lower energy input. This physical contact is appropriate for the unquestionable unloading of Mln medications to the intended location. The reactivity is higher in BNNSs and BNCNSs, while the stability is higher in BNCNCs. The recovery time shows a shorter time for BNNSs and BNCNSs, while BNCNC shows a potential desorption time in higher temperature. These conclusions are corroborated by the results of the quantum theory of atoms in molecules (QTAIM). After the interaction analysis, it was observed that the BNCNCs can act as potential carriers for the melphalan. From dipole moment analysis, all three nanostructures show a high hydrophilic nature but quite higher in BNCNCs after doping in both media. Overall, all the structures show the potential carrier for melphalan drug., Methods: The quantum mechanical approach, or DFT, has been used to study the fundamental structural, electrical, thermodynamic, and other aspects of proposed structures to develop an acceptable Mln drug detector. The adsorbate and all adsorbents were optimized via the hybrid B3LYP functional and the 6-311G +  + (2d, p) basis set approach prior to the adsorption process. The Gaussian 09 package was used at 298 K as the constant temperature and 1 atm as the constant pressure. The structures are examined using the same functional models for solvation analysis-6-311 G +  + (2d, p) and B3LYP-as well as the polarized continuum model (PCM) model as the foundation set. Density of states was studied using GaussSum 3.0 software. The interaction studies QTAIM and RDG were studied using VMD and Multiwfn software., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Triple negative breast cancer (TNBC) is a notoriously difficult disease to treat, and many of the existing TNBC chemotherapeutics lack tumor selectivity and the capability for simultaneously visualizing and monitoring their own activity in the biological context. However, TNBC cells have been known to generate high levels of reactive oxygen species (ROS), such as hydrogen peroxide (H 2 O 2 ). To this end, three novel small molecule theranostics 1a, 1c, and 2 consisting of both H 2 O 2 -responsive nitrogen mustard prodrug and profluorophore character have been designed, synthesized, and evaluated as targeted cancer therapeutics and bioimaging agents. The three theranostics comprise of boronate esters that deactivate nitrogen mustard functional groups and fluorophores but allow their selective activation through H 2 O 2 -specific oxidative deboronation for the release of the active drug and fluorophore. The three theranostics demonstrated H 2 O 2 -inducible DNA-alkylating capability and fluorescence turn-on properties in addition to selective anticancer activity. They are particularly effective in killing TNBC MDA-MB-468 cells with high H 2 O 2 level while safe to normal epithelial MCF-10A cell. The conjugated boron-masked fluorophores in 1c and 2 are highly responsive towards H 2 O 2 , which enabled tracking of the theranostics in living cellular mitochondria and nucleus organelles. The three theranostics 1a, 1c, and 2 are capable of both selective release of the active drug to take effect in H 2 O 2 -rich cancer sites and simultaneously monitoring its activity. This single molecule system is of utmost importance to understand the function, efficacy, and mechanism of the H 2 O 2 -activated prodrugs and theranostics within the living recipient., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Xiaohua Peng reports financial support was provided by National Institutes of Health. Xiaohua Peng has patent pending to University of Wisconsin Milwaukee Research Foundation. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Timely diagnosis and therapy of Alzheimer's disease remains one of the greatest questions in medicinal chemistry of neurodegenerative disease. The lack of low-cost sensors capable of reliable detection of structural changes in AD-related proteins is the driving factor for the development of novel molecules with affinity for AD hallmarks. The development of cheap, safe diagnostic methods is a highly sought-after area of research. Optical fluorescent probes are of great interest due to their non-radioactivity, low cost, and ability of the real-time visualization of AD hallmarks. Boron dipyrromethene (BODIPY)-based fluorophore is one promising fluorescent unit for in vivo labeling due to its high photostability, easy modification, low toxicity, and cell-permeability. In recent years, many fluorescent BODIPY-based probes capable of Aβ plaque, Aβ soluble oligomers, neurofibrillary tangles (NFT) optical detection, as well as probes with copper ion chelating units and viscosity sensors have been developed. In this review, we summarized BODIPY derivatives as fluorescent sensors capable of detecting pathological features of Alzheimer's disease, published from 2009 to 2023, as well as their design strategies, optical properties, and in vitro and in vivo activities., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Alexander Erofeev reports financial support was provided by National University of Science and TechnologyMISIS. Olga Krasnovskaya reports a relationship with National University of Science and Technology MISIS that includes: employment. There is no conflict of interest to declare. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus continues to cause severe disease and deaths in many parts of the world, despite massive vaccination efforts. Antiviral drugs to curb an ongoing infection remain a priority. The virus-encoded 3C-like main protease (MPro; nsp5) is seen as a promising target. Here, with a positive selection genetic system engineered in Saccharomyces cerevisiae using cleavage and release of MazF toxin as an indicator, we screened in a robotized setup small molecule libraries comprising ~2,500 compounds for MPro inhibitors. We detected eight compounds as effective against MPro expressed in yeast, five of which are characterized proteasome inhibitors. Molecular docking indicates that most of these bind covalently to the MPro catalytically active cysteine. Compounds were confirmed as MPro inhibitors in an in vitro enzymatic assay. Among those were three previously only predicted in silico ; the boron-containing proteasome inhibitors bortezomib, delanzomib, and ixazomib. Importantly, we establish reaction conditions in vitro preserving the MPro-inhibitory activity of the boron-containing drugs. These differ from the standard conditions, which may explain why boron compounds have gone undetected in screens based on enzymatic in vitro assays. Our screening system is robust and can find inhibitors of a specific protease that are biostable, able to penetrate a cell membrane, and are not generally toxic. As a cellular assay, it can detect inhibitors that fail in a screen based on an in vitro enzymatic assay using standardized conditions, and now give support for boron compounds as MPro inhibitors. This method can also be adapted for other viral proteases.IMPORTANCEThe coronavirus disease 2019 (COVID-19) pandemic triggered the realization that we need flexible approaches to find treatments for emerging viral threats. We implemented a genetically engineered platform in yeast to detect inhibitors of the virus's main protease (MPro), a promising target to curb severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Screening molecule libraries, we identified candidate inhibitors and verified them in a biochemical assay. Moreover, the system detected boron-containing molecules as MPro inhibitors. Those were previously predicted computationally but never shown effective in a biochemical assay. Here, we demonstrate that they require a non-standard reaction buffer to function as MPro inhibitors. Hence, our cell-based method detects protease inhibitors missed by other approaches and provides support for the boron-containing molecules. We have thus demonstrated that our platform can screen large numbers of chemicals to find potential inhibitors of a viral protease. Importantly, the platform can be modified to detect protease targets from other emerging viruses., Competing Interests: The authors declare no conflict of interest.

A common goal in mass spectrometry-based chemoproteomics is to directly measure the site of conjugation between the target protein and the small molecule ligand. However, these experiments are inherently challenging due to the low abundance of labeled proteins and the difficulty in identifying modification sites using standard proteomics software. Reporter tags that either generate signature fragment ions or isotopically encode target peptides can be used for the preemptive discovery of labeled peptides even in the absence of identification. We investigated the potential of BODIPY FL azide as a click chemistry enabled chemoproteomics reagent due to the presence of boron and the unique 1:4 natural abundance ratio of 10 B: 11 B. The isotopes of boron encode BODIPY-labeled peptides with a predictable pattern between the monoisotopic (M) and M+1 peaks. BODIPY-labeled peptides were identified in MS1 spectra using an R script that filters for the signature 10 B: 11 B intensity ratio and mass defect. Application of the boron detection script resulted in three times the labeled peptide coverage achieved for a BODIPY-conjugated BSA sample compared with untargeted data-dependent acquisition sequencing. Furthermore, we used the inherent HF neutral loss signature from BODIPY to assist with BODIPY-modified peptide identification. Finally, we demonstrate the application of this approach using the BODIPY-conjugated BSA sample spiked into a complex E. coli . digest. In summary, our results show that the commercially available BODIPY FL azide clicked to alkyne-labeled peptides provides a unique isotopic signature for pinpointing the site(s) of modification with the added potential for on- or off-line UV or fluorescence detection.

Anticancer drugs inhibit DNA replication by intercalating between DNA base pairs, forming covalent bonds with nucleotide bases, or binding to the DNA groove. To develop safer drugs, novel molecular structures with alternative binding mechanisms are essential. Stable boron hydrides offer a promising alternative for cancer therapy, opening up additional options like boron neutron capture therapy based on 10 B and thermal neutron beams or proton boron fusion therapy using 11 B and proton beams. These therapies are more efficient when the boron compound is ideally located inside cancer cells, particularly in the nucleus. Current cancer treatments often utilize small, polycyclic, aromatic, planar molecules that intercalate between ds-DNA base pairs, requiring only a spacing of approximately 0.34 nm. In this paper, we demonstrate another type of intercalation. Notably, [3,3'-Fe(1,2-C 2 B 9 H 11 ) 2 ] - , ([ o -FESAN] - ), a compact 3D molecule measuring 1.1 nm × 0.6 nm, can as well intercalate by strong non-bonding interactions preferentially with guanine. Unlike known intercalators, which are positive or neutral, [ o -FESAN] - is a negative species and when an [ o -FESAN] - molecule approaches the negatively charged DNA phosphate chain an anion-anion interaction consistently anti-electrostatic via C cluster -H⋯O-P bonds occurs. Then, when more molecules approach, an elongated outstandingly self-assembled structure of [ o -FESAN] - -[ o -FESAN] - forms moving anions towards the interthread region to interact with base pairs and form aggregates of four [ o -FESAN] - anions per base pair. These aggregates, in this environment, are generated by C cluster -H⋯O-C, N-H⋯H-B and C cluster -H⋯H-B interactions. The ferrabis(dicarbollide) boron-rich small molecules not only effectively penetrate the nucleus but also intercalate with ds-DNA, making them promising for cancer treatment. This amphiphilic anionic molecule, used as a carrier-free drug, can enhance radiotherapy in a multimodal perspective, providing healthcare professionals with improved tools for cancer treatment. This work demonstrates these findings with a plethora of techniques.

NH 2 -MIL-125(Ti) materials had great potential for photocatalytic applications but had low activity due to exciton effect and narrow absorption range of visible light. The surface oxygen-containing negative functional groups of boron nitride quantum dots (BNQDs) could overcome these defects, but due to the low load capacity, a higher specific surface area of the substrate was usually required. In this paper, a hollow Ti-MOF material was developed by etching technology. The hollow structure formed by tannic acid etching broadened the absorption range of visable light and provided more alternative surfaces for loading BNQDs. The 85.2% of high tetracycline (TC) removal efficiency for the best sample (BNQDs-5@20-Ti-MOF + PMS) was obtained, which was about 56.8 and 1.9 times of the 20-Ti-MOF and BNQDs-5@20-Ti-MOF, respectively. BNQDs-5@20-Ti-MOF + PMS system showed a great TC degradation efficiency in a wide pH range (pH = 5-9). In addition, reaction temperature and the inorganic ions did not show significant inhibition effect for TC removal. Both free radical and non-free radical pathways were involved in the TC degration by BNQDs-5@20-Ti-MOF + PMS system, among which O 2 •- and 1 O 2 played the key roles. Interestingly, multiple 1 O 2 production paths contributed to the high efficiency and stability of BNQDs-5@20-Ti-MOF + PMS system. This study revealed a reasonable combination of Ti-MOF and BNQDs, which provided a new efficient photocatalyst for environmental remediation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

This study evaluated the effects of two chlorophyll derivatives, sodium copper chlorophyllin (Cu-Chl) and sodium iron chlorophyllin (Fe-Chl), on the bond strength between a self-curing luting agent (4-META/MMA-TBB resin) and dentin. Five aqueous primers containing 35% 2-hydroxyethylmethacrylate with 0.007% Cu-Chl, 0.07% Cu-Chl, 0.007% Fe-Chl, 0.07% Fe-Chl, or neither Cu-Chl nor Fe-Chl (no-Chl) were prepared. The extracted human dentin surfaces were etched with 10% phosphoric acid (10PA), primed, and bonded to a resin block using the 4-META/MMA-TBB resin. A conventional etching agent (10-3) and 10PA without primer (PA/no-primer) were used as controls. The microtensile bond strength was determined after 48 h. The arithmetic medians for 20 stick specimens were calculated and statistically analyzed using a nonparametric Steel-Dwass test (α = 0.05). The maximum bond strength was achieved in the 0.007% Cu-Chl group, followed by those in the 0.07% Cu-Chl, 0.07% Fe-Chl, 10-3, 0.007% Fe-Chl, no-Chl, and PA/no-primer groups. No significant difference was observed between 0.007% Fe-Chl, 0.07% Fe-Chl, and 10-3. The bond strength to dentin etched with 10PA was influenced by the type and concentration of the chlorophyll derivatives applied. Cu-Chl rather than Fe-Chl should be useful as a component of surface treatment agents for bonding 4-META/MMA-TBB resin to dentin., (© 2024 Scandinavian Division of the International Association for Dental Research. Published by John Wiley & Sons Ltd.)

Lipid droplets (LDs) are organelles associated with lipid storage and energy metabolism, thus, their morphology and quantity are of significant research interest. While commercially available BODIPY dye effectively labels LDs in various cell types, it also labels lysosome-related organelles (LROs) in C. elegans, leading to non-specific LD quantification. Here, we report that the fluorescent signals of BODIPY exhibit distinct fluorescence lifetime patterns for LROs and LDs, which can be captured, visualized, and filtered by fluorescence lifetime imaging microscopy. Furthermore, we proposed and validated a method based on fluorescence lifetime that can improve the accuracy of fat storage quantification in BODIPY vital-staining worms, which holds broad applications, including rapid and accurate LD quantification in forward genetic screening. Additionally, our method enables observing dynamic LD-LRO interactions in living worms, a unique capability of BODIPY vital staining. Our findings highlight distinct BODIPY fluorescence lifetime characteristics of LDs and LROs, providing a valuable tool for future research on LDs, LROs, or their interactions., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Glioblastoma is a highly aggressive glioma with limited treatment options. Boron neutron capture therapy (BNCT) offers a promising approach for refractory cancers, utilizing boron-10 ( 10 B) and thermal neutrons to generate cytotoxic particles. Effective BNCT depends on selective targeting and retention of 10 B in tumors. Current BNCT drugs face issues with rapid clearance and poor tumor accumulation. To address this, we developed gold nanoparticles (AuNPs) functionalized with cyclic arginine-glycine-aspartic acid (cRGD) peptides as a nanocarrier for Sodium Mercaptododecaborate (BSH), resulting in AuNPs-BSH&PEG-cRGD. In vitro , AuNPs-BSH&PEG-cRGD increased 10 B content in GL261 glioma cells by approximately 2.5-fold compared to unmodified AuNPs-BSH&PEG, indicating enhanced targeting due to cRGD's affinity for integrin receptor α v β 3 . In a subcutaneous glioma mouse model, 6 h post-intratumoral administration, the 10 B concentration in tumors was 17.98 μg/g for AuNPs-BSH&PEG-cRGD, significantly higher than 0.45 μg/g for BSH. The tumor-to-blood (T/B) and tumor-to-normal tissue (T/N) ratios were also higher for AuNPs-BSH&PEG-cRGD, suggesting improved targeting and retention. This indicates that AuNPs-BSH&PEG-cRGD may enhance BNCT efficacy and minimize normal tissue toxicity. In summary, this study provides a novel strategy for BSH delivery and may broaden the design vision of BNCT nano-boron capture agents.

Combining thermal conductive fillers and flexible polymers is an agile approach to fabricating composites with heat-conducting performance. However, the thermal conductivity of the composites is hard to reach an equal level to the functional fillers. The mainspring is that the thermally conductive pathways within the composite could not be well-constructed due to the air-induced interface thermal resistance. Herein, inspired by the plant cell wall structure, polyvinyl alcohol (PVA) with abundant hydroxyl groups was adopted as a binder for boosting the thermally conductive pathways construction between cellulose nanofiber (CNF) and alkalized hexagonal boron nitride (BN-OH), also for strengthening the mechanical performance of the composite. The results showed that the tensile strength and through-plane thermal conductivity of the composite were high up to 91.0 MPa and 2.2 W m -1  K -1 at 40 wt% PVA content, exhibiting 121 % and 450 % enhancements compared to pure CNF film (41.2 MPa and 0.4 W m -1  K -1 ). Moreover, the composite also presented high thermal stability (decomposition temperature of onset was 218 °C) and good hydrophobicity properties. Overall, this study innovatively proposes an idea for enhancing the thermal conductivity and improving the mechanical properties of the composite, which is indispensable for developing thermal management materials for next-generation electronics., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The impacts of dimethylation of 4-Amino-1,8-Naphthalimide (ANI) on its photophysical properties are reported. The resulting 4-DiMe-ANI displays completely different fluorescence properties, conferring it ability to selectively label lipid droplets in living cells. A comprehensive photophysical study revealed that this selectivity arises from an Internal Charge Transfer favored in lipophilic media to the detriment of a non-emissive TICT in more polar media. This results in a very high "LDs/Cytosol" signal ratio, enabling LDs to be imaged with an excellent signal-to-noise ratio, and positioning its performance above that of the BODIPY 493/503 commonly used to image LDs., (© 2024 The Authors. ChemBioChem published by Wiley-VCH GmbH.)

Unveiling the intricate relationship between cancer and Golgi viscosity remains an arduous endeavor, primarily due to the lack of Golgi-specific fluorescent probes tailored for viscosity measurement. Considering this formidable obstacle, we have triumphed over the challenge by devising a bespoke Golgi-specific viscosity probe, aptly named GOL-V. This ingenious innovation comprises the viscosity rotor BODIPY intricately tethered to the Golgi-targeting moiety benzsulfamide. GOL-V exhibits remarkable sensitivity to fluctuations in viscosity, the fluorescence intensity of GOL-V increased 114-fold when the viscosity value was increased from 2.63 to 937.28 cP. Owing to its remarkable capacity to suppress the TICT state under conditions of heightened viscosity. Moreover, its efficacy in sensitively monitoring Golgi viscosity alterations within living cells is also very significant. Astonishingly, our endeavors have culminated in not only the visualization of Golgi viscosity at the cellular and tissue levels but also in the clinical tissue samples procured from cancer patients. Harnessing the prowess of GOL-V, we have successfully demonstrated that Golgi viscosity could serve as a discerning marker for detecting the presence of cancer. The convergence of these exceptional attributes firmly establishes GOL-V as an immensely potent instrument, holding immense potential in the realm of cancer diagnosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Photodynamic therapy (PDT) is a minimally invasive method for cancer treatment, one of the effects of which is the oxidation of membrane lipids. However, changes in biophysical properties of lipid membranes during PDT have been poorly explored. In this work, we investigated the effects of PDT on membrane microviscosity in cancer cells in the culture and tumor xenografts. Membrane microviscosity was visualized using fluorescence lifetime imaging microscopy (FLIM) with a viscosity-sensitive rotor BODIPY2. It was found that PDT using chlorine e6-based photosensitizer Photoditazine caused a quick, steady elevation of membrane microviscosity both in cellulo and in vivo. The proposed mechanisms responsible for the increase in microviscosity was lipid peroxidation by reactive oxygen species that resulted in a decrease of phosphatidylcholine and the fraction of unsaturated fatty acids in the membranes. Our results suggest that the increased microviscosity is an important factor that contributes to tumor cell damage during PDT., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Marina Shirmanova reports financial support was provided by Russian Science Foundation. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Photoimmunotherapy represents an innovative approach to enhancing the efficiency of immunotherapy in cancer treatment. This approach involves the fusion of immunotherapy and phototherapy (encompassing techniques like photodynamic therapy (PDT) and photothermal therapy (PTT)). Boron-dipyrromethene (BODIPY) has the potential to trigger immunotherapy owing to its excellent PD and PT efficiency. However, the improvements in water solubility, bioavailability, PD/PT combined efficiency, and tumor tissue targeting of BODIPY require introduction of suitable carriers for potential practical application. Herein, a disulfide bond-based hollow mesoporous organosilica (HMON) with excellent biocompatibility and GSH-responsive degradation properties was used as a carrier to load a bithiophene Aza-BODIPY dye (B5), constructing a sample chemotherapy reagent-free B5@HMON nanoplatform achieving triple-synergistic photoimmunotherapy. HMON, involving disulfide bond, is utilized to improve water solubility, tumor tissue targeting, and PD efficiency by depleting GSH and enhancing host-guest interaction between B5 and HMO. The study reveals that HMON's large specific surface area and porous properties significantly enhance the light collection and oxygen adsorption capacity. The HMON's rich mesoporous structure and internal cavity achieved a loading rate of B5 at 11 %. It was found that the triple-synergistic nanoplatform triggered a stronger anti-tumor immune response, including tumor invasion, cytokine production, calreticulin translocation, and dendritic cell maturation, eliciting specific tumor-specific immunological responses in vivo and in vitro. The BALB/c mouse model with 4T1 tumors was used to assess tumor suppression efficiency in vivo, showing that almost all tumors in the B5@HMON group disappeared after 14 days. Such a simple chemotherapy reagent-free B5@HMON nanoplatform achieved triple-synergistic photoimmunotherapy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

We scrutinized the impact of doping of X atoms (X = Fe, Co, Ni, Cu, and Zn) on the metformin (MF) drug delivery performance of a BP nanotube (BPNT) using density functional B3LYP calculations. The pristine BPNT was not ideal for the drug delivery of MF because of a weak interaction between the drug and nanotube. Doping of the Zn, Cu, Ni, Co, and Fe into the BPNT surface raised the adsorption energy of MF from -5.3 to -29.1, -28.7, -29.8, -32.1, and -26.9 kcal/mol, respectively, demonstrating that the sensitiveness of the metal-doped BPNT increased after increasing the radius atomic of metals. Ultimately, there was an increase in the adhesion performance and capacity of the MF after X (especially Co atom) doping, making the nanotube suitable for MF drug delivery. The mechanism of MF reaction with the BPNT changed from covalent bonding in the natural environment to hydrogen bonding in the cancerous cells with high acidity.

Photodynamic therapy (PDT) is a clinically-approved cancer treatment that is based on production of cytotoxic reactive oxygen species to induce cell death. However, its efficiency depends on distribution of photosensitizer (PS) and depth of light penetration through the tissues. Tendency of pathological cancer tissues to exhibit lower pH than healthy tissues inspired us to explore dual-targeted pH-activatable photosensitizers based on tunable near-infrared (NIR) boron-dipyrromethene (BODIPY) dyes. Our BODIPY PSs were designed to carry three main attributes: (i) biotin or cRGD peptide as an effective cancer cell targeting unit, (ii) amino moiety that is protonated in acidic (pH <6.5) conditions for pH-activation of the PS based on photoinduced electron transfer (PET) and (iii) hydrophilic groups enhancing the water solubility of very hydrophobic BODIPY dyes. Illumination of such compounds with suitable light (>640nm) allowed for high phototoxicity against HeLa (α v β 3 integrin and biotin receptor positive) and A549 (biotin receptor positive) cells compared to healthy MRC-5 (biotin negative) cells. Moreover, no dark toxicity was observed on selected cell lines (>10 μM) providing promising photosensitizers for tumour-targeted photodynamic therapy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Oxidative stress is a cellular disorder implicated in various severe diseases and redox biology and represents an important field of research for the last decades. One of the major consequences of oxidative stress is the carbonylation of proteins, which is also a reliable marker to assess protein oxidative modifications. Accumulation of carbonylated proteins has been associated with aging and age-related diseases and can ultimately causes cell death. Detection of these oxidative modifications is essential to understand and discover new treatments against oxidative stress. We describe the design and the synthetic pathway of new BODIPY fluorescent probes functionalized with hydrazide function for protein carbonyl labeling to improve existing methodologies such as 2D-Oxi electrophoresis. Hydrazide BODIPY analogues show very good fluorescent properties such as NIR emission up to 633 nm and quantum yield up to 0.88. These new probes were validated for the detection and quantification of carbonylated proteins with 2D-Oxi electrophoresis using mouse muscle protein extracts, as well as both flow cytometry and microscopy using oxidant stressed C2 C12 cells., (© 2024 The Authors. ChemBioChem published by Wiley-VCH GmbH.)

Aza-BODIPYs represent a class of fluorophores in which the π-conjugated system is rigidified and stabilized by a boron atom. A promising strategy to enhance their fluorescence properties involves replacing the boron atom with a metal ion. Here, we describe the synthesis and characterization of a water-soluble derivative where the metal is a gallium(III) ion, termed WazaGaY (water-soluble aza-GaDIPY). Water solubility is ensured by two ammonium substituents, inducing a bathochromic shift and a significant increase in quantum yield compared to that of the dimethylamino analog. The cellular behavior of WazaGaY-1 was observed across different tumor cells. In vivo , the distribution and safety profiles were determined, and tumor uptake was assessed in various tumor types. Following intravenous injection, WazaGaY-1 enabled clear discrimination of tumors engrafted subcutaneously in mice with high tumor-to-muscle ratios (ranging from 7 to 20), even in the absence of specific conjugation. Its potential as a contrast agent for fluorescence-guided surgery was confirmed.

The disintegration of nanoparticles and drug release are important and imperative for nanoparticle formulations of therapeutic agents. However, quantitatively monitoring the drug release of nanomedicines is a major challenge. In this work, boron-dipyrromethene (BDP) was applied as a model drug to study the disassembly of nanoparticles and drug release. BDP dimers with disulfide and ester bonds were synthesized, and their nanoparticles were made. The accurate analysis of bond breaking in BDP nanoparticles could not be realized by using confocal laser scanning microscopy. Hence, the possible products after bond cleavage were quantified by using liquid chromatography tandem mass spectrometry (LC-MS/MS). BDP nanoparticles could be endocytosed into cancer cells, and the disulfide bonds and ester bonds were broken to promote the disassociation of nanoparticles and BDP release. Then, near-infrared BDP nanoparticles were investigated in live mice by near-infrared fluorescence imaging and LC-MS/MS. The release of BDP was low (<10%) and BDP maintained the original dimer structure in vivo , which showed that the bond breaking for BDP nanoparticles was difficult in vivo . These results could help us understand the breaking law of disulfide bonds and ester bonds in nanoparticles and are beneficial for developing practical new drug formulations.

Rheumatoid arthritis (RA) is a debilitating autoimmune disease characterized by chronic joint inflammation and cartilage damage. Current therapeutic strategies often result in side effects, necessitating the development of targeted and safer treatment options. This study introduces a novel nanotherapeutic system, 2-APB@DGP-MM, which utilizes macrophage membrane (MM)-encapsulated nanoparticles (NPs) for the targeted delivery of 2-Aminoethyl diphenylborinate (2-APB) to inflamed joints more effectively. The NPs are designed with a matrix metalloproteinase (MMP)-cleavable peptide, allowing for MMP-responsive drug release within RA microenvironment. Comprehensive in vitro and in vivo assays confirmed the successful synthesis and loading of 2-APB into the DSPE-GPLGVRGC-PEG (DGP) NPs, as well as their ability to repolarize macrophages from a pro-inflammatory M1 to an anti-inflammatory M2 phenotype. The NPs demonstrated high biocompatibility, low cytotoxicity, and enhanced cellular uptake. In a collagen-induced arthritis (CIA) mouse model, intra-articular injection of 2-APB@DGP-MM significantly reduced synovial inflammation and cartilage destruction. Histological analysis corroborated these findings, demonstrating marked improvements in joint structure and delayed disease progression. Above all, the 2-APB@DGP-MM nanotherapeutic system offers a promising and safe approach for RA treatment by modulating macrophage polarization and delivering effective agents to inflamed joints., (© 2024. The Author(s).)

Photodynamic therapy (PDT) can destroy tumor cells by generating singlet oxygen ( 1 O 2 ) under light irradiation, which is limited by the hypoxia of the neoplastic tissue. Chemodynamic therapy (CDT) can produce toxic hydroxyl radical (⋅OH) to eradicate tumor cells by catalytic decomposition of endogenous hydrogen peroxide (H 2 O 2 ), the therapeutic effect of which is highly dependent on the concentration of H 2 O 2 . Herein, we propose a BODIPY-ferrocene conjugate with a balanced 1 O 2 and ⋅OH generation capacity, which can serve as a high-efficiency antitumor agent by combining PDT and CDT. The ferrocene moieties endow the as-prepared conjugates with the ability of chemodynamic killing of tumor cells. Moreover, combined PDT/CDT therapy with improved antitumor efficiency can be realized after exposure to light irradiation. Compared with the monotherapy by PDT or CDT, the BODIPY-ferrocene conjugates can significantly increase the intracellular ROS levels of the tumor cells after light irradiation, thereby inducing the tumor cell apoptosis at low drug doses. In this way, a synergistic antitumor treatment is achieved by the combination of PDT and CDT., (© 2024 Wiley-VCH GmbH.)

Small-molecule sensors that are selective for particular sugars are rare. The synthesis of BODIPYs appended with two boronic acid units is reported, alongside cellular staining/labelling and turn-on fluorescence binding data for carbohydrates. The structural frameworks were designed using computational methods, leaning on the chelation characteristics of bis(boronic acids) and the photophysical properties of BODIPYs. Selective binding to glucose is demonstrated via emission and absorption methods, and the challenges of using NMR data for studying carbohydrate binding are discussed. Furthermore, crystal structures, cell permeability and imaging properties of the BODIPYs appended with two boronic acid units are described. This work presents boronic-acid-appended BODIPYs as a potential framework for tunable carbohydrate sensing and chemical biology staining.

Using the principle of "Magic Bullet", a cisplatin-derived platinum(IV) prodrug heterobimetallic Pt(IV)-Ru(II) complex, cis,cis,trans -[Pt(NH 3 ) 2 Cl 2 {Ru(tpy-BODIPY)(tpy-COO)}(biotin)]Cl 2 ( Pt-Ru-B , 2 ), having two axial ligands, namely, biotin as water-soluble B-vitamin for enhanced cellular uptake and a BODIPY-ruthenium(II) ( Ru-B , 1 ) photosensitizer having N , N , N -donor tpy (4'-phenyl-2,2':6',2″-terpyridine) bonded to boron-dipyrromethene (BODIPY), is developed as a "Platin Bullet" for targeted photodynamic therapy (PDT). Pt-Ru-B exhibited intense absorption near 500 nm and emission near 513 nm (λ ex = 488 nm) in a 10% dimethyl sulfoxide-Dulbecco's phosphate-buffered saline medium (pH 7.2). The BODIPY complex on light activation generates singlet oxygen as the reactive oxygen species (ROS) giving a quantum yield (Φ Δ ) of ∼0.64 from 1,3-diphenylisobenzofuran experiments. Pt-Ru-B exhibited preferential cellular uptake in cancer cells over noncancerous cells. The dichlorodihydrofluorescein diacetate assay confirmed the generation of cellular ROS. Confocal images revealed its mitochondrial internalization. Pt-Ru-B showed submicromolar photocytotoxicity in visible light (400-700 nm) in A549 and multidrug-resistant MDA-MB-231 cancer cells. It remained nontoxic in the dark and less toxic in nontumorigenic cells. Cellular apoptosis and alteration of the mitochondrial membrane potential were evidenced from the respective Annexin V-FITC/propidium iodide assay and JC-1 dye assay. A wound healing assay using A549 cells and Pt-Ru-B revealed inhibition of cancer cell migration, highlighting its potential as an antimetastatic agent.

Functionalized few-layer borophene (FFB) was prepared using gallnut extract and coffee waste extract as natural exfoliating and stabilizing agents in an environmentally friendly ultrasonic and high shear exfoliation. Here, a facile precipitation method was employed to grow iron oxide nanoparticles doped with cerium (Ce-FeONPs) onto the surface of FFB. This intriguing combination of materials yielded Ce-FeONPs nanoparticles that exhibited exceptional peroxidase-like activity, efficiently catalyzing the conversion of 3,3',5,5'-tetramethylbenzidine (TMB) to a blue oxidized TMB (oxTMB) in the presence of hydrogen peroxide (H 2 O 2 ). Additionally, the introduction of FFB contributes a reducibility effect to the catalytic oxidation of TMB, facilitating the restoration of the oxTMB to TMB. Thus, FFB-Ce-FeONPs showcase intriguing properties encompassing both oxidative and reductive characteristics, suggesting their potential as a reagent for repeated detection of H 2 O 2 . Moreover, a colorimetric sensing system enabled the liner detection of H 2 O 2 spanning a concentration range from 0.08 to 1 mM, with a detection limit of 0.03 mM. Noteworthily, FFB-Ce-FeONPs demonstrated sustained efficacy over ten successive recycling cycles, as indicated by consistent slopes and observable color changes. In summary, this work reports the first application of nanoenzymes in repetitive H 2 O 2 detection. Even after ten multiple cycles, the detection limit remains virtually unaltered, underscoring the robustness and enduring effectiveness of the engineered nanomaterial. The proposed simultaneous oxidation and reduction strategies for detecting H 2 O 2 showed a commendable capability in ten cycles of H 2 O 2 detection, thus providing a promising approach in the field of H 2 O 2 detection., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

In this work, various novel pyridinyl- and pyridinium-modified Aza-BODIPY PSs were designed and constructed based on monoiodo Aza-BODIPY PSs ( BDP-4 and BDP-15 ) in an attempt to construct "structure-inherent organelles-targeted" PSs to endow potential organelle-targeting ability. Pyridinyl PSs displayed potent photodynamic efficacy, and monorigidified PSs were very effective. The monorigidified PS 20 with meta -pyridinyl moiety displayed the most potent photoactivity and negligible dark toxicity with a favorable dark/phototoxicity ratio (>4800). To our surprise, monorigidified PS with meta -pyridinyl moiety (e.g., 20 ) was lipid droplet-targeted. 20 showed good cellular uptake and intracellular ROS generation compared with BDP-15 . The preliminary cell death process exploration indicated that 20 resulted in lipid peroxidation and induced cell death through an iron-independent ferroptosis-like cell death pathway. In vivo antitumor efficacy experiments manifested that 20 significantly inhibited tumor growth and outperformed BDP-15 and Ce6 even under a single low-dose light irradiation (30 J/cm 2 ).

With their low immunogenicity and excellent deliverability, extracellular vesicles (EVs) are promising platforms for drug delivery systems. In this study, hydrophobic molecule loading techniques were developed via an exchange reaction based on supramolecular chemistry without using organic solvents that can induce EV disruption and harmful side effects. To demonstrate the availability of an exchanging reaction to prepare drug-loading EVs, hydrophobic boron cluster carborane (CB) was introduced to EVs (CB@EVs), which is expected as a boron agent for boron neutron capture therapy (BNCT). The exchange reaction enabled the encapsulation of CB to EVs without disrupting their structure and forming aggregates. Single-particle analysis revealed that an exchanging reaction can uniformly introduce cargo molecules to EVs, which is advantageous in formulating pharmaceuticals. The performance of CB@EVs as boron agents for BNCT was demonstrated in vitro and in vivo. Compared to L-BPA, a clinically available boron agent, and CB delivered with liposomes, CB@EV systems exhibited the highest BNCT activity in vitro due to their excellent deliverability of cargo molecules via an endocytosis-independent pathway. The system can deeply penetrate 3D cultured spheroids even in the presence of extracellular matrices. The EV-based system could efficiently accumulate in tumor tissues in tumor xenograft model mice with high selectivity, mainly via the enhanced permeation and retention effect, and the deliverability of cargo molecules to tumor tissues in vivo enhanced the therapeutic benefits of BNCT compared to the L-BPA/fructose complex. All of the features of EVs are also advantageous in establishing anticancer agent delivery platforms.

Lysosome imaging plays an important role in diagnosing many diseases and understanding various intracellular processes. Recently, B0 was reported as a fluorescent probe capable of detecting lysosomal viscosity changes. BODIPY is fused into the molecule as a bridge between the acceptor and donor components of B0, yielding nine new B molecules. Computational design and analysis of their optoelectronic properties were conducted to evaluate their effectiveness as fluorescent probes for lysosome imaging, with a specific target of HSA inside lysosomes. Optimized geometries reveal excellent π electron delocalization, resulting in nearly planar molecular structures. Frontier molecular orbital analysis suggests intramolecular charge transfer, along with π-π* transitions, from donor to bridge. TD-DFT calculations were performed to study absorption properties in the solvent phase, with B3PW91 showing good agreement with experiments. Molecular docking studies indicate that B derivatives can bind with HSA, and molecular dynamics simulations confirm their HSA targeting ability. This investigation highlights the introduction of BODIPY as a bridge for developing new probes capable of producing NIR fluorescence for bio-imaging, aiding in disease diagnosis.

The twist fusion of a benzothiophene group and the introduction of a 4-methyloxystyryl donor group to the BODIPY core resulted in large spin-orbit coupling values and smaller singlet-triplet energy gaps for the novel infrared absorbed photosensitizers named BSBDP. They show a high reactive oxygen species efficiency exceeding 69% and a fluorescence quantum yield of 23% and are successfully applied in imaging-guided photodynamic therapy in vitro and in vivo .

Aggrephagy describes lysosomal transport and degradation of protein aggregates via cellular macroautophagy, a key mechanism to prevent neurodegenerative diseases. Here, we develop a dual-probe method to visualize the aggrephagy process and resolve its viscosity heterogeneity using fluorescence lifetime imaging (FLIM). The dual-probe system consists of (1) a near-infrared lysosomal targeting FLIM probe (Lyso-P1) that is derived from a rhodamine scaffold with a tailored p K a value to accommodate an acidic lysosomal environment and (2) a green BODIPY-based FLIM probe (Agg-P2) that reports on degradation of cellular aggregates via HaloTag. Both probes exhibit acid-resistant, viscosity-dependent fluorescence intensity and lifetime (τ) responses, which are ready for intensity- and FLIM-based imaging. Photochemical, theoretical, and biochemical characterizations reveal the probes' mechanism-of-actions. In cells, we exploit Lyso-P1 and Agg-P2 to simultaneously quantify both lysosomal and protein aggegates' viscosity changes upon the aggrephagy process via FLIM. We reveal orthogonal changes in microenvironmental viscosities and morphological heterogeneity upon various cellular stresses. Overall, we provide an imaging toolset to quantitatively study aggrephay, which may benefit screening of aggrephay modulators for disease intervention.

A range of novel BODIPY derivatives with a tripodal aromatic core was synthesized and characterized spectroscopically. These new fluorophores showed promising features as probes for in vitro assays in live cells and offer strategic routes for further functionalization towards hybrid nanomaterials. Incorporation of biotin tags facilitated proof-of-concept access to targeted bioconjugates as molecular probes. Computational explorations using DFT and TD-DFT calculations identified the most stable tripodal linker conformations and predicted their absorption and emission behavior. The uptake and speciation of these molecules in living prostate cancer cells was imaged by single- and two-photon excitation techniques coupled with two-photon fluorescence lifetime imaging (2P FLIM)., (© 2024 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

Acute liver injury (ALI) is a frequent and devastating liver disease that has been made more prevalent by the excessive use of chemicals, drugs, and alcohol in modern life. Hypochlorous acid (HClO), an important biomarker of oxidative stress originating mainly from the mitochondria, has been shown to be intimately connected to the development and course of ALI. Herein, a novel BODIPY-based NIR ratiometric fluorescent probe Mito-BS was constructed for the specific recognition of mitochondrial HClO. The probe Mito-BS can rapidly respond to HClO within 20 s with a ratiometric fluorescence response (from 680 nm to 645 nm), 24-fold fluorescence intensity ratio enhancement (I 645 /I 680 ), a wide pH adaptation range (5-9) and the low detection limit (31 nM). The probe Mito-BS has been effectively applied to visualize endogenous and exogenous HClO fluctuations in living zebrafish and cells based on its low cytotoxicity and prominent mitochondria-targeting ability. Furthermore, the fluorescent probe Mito-BS makes it possible to achieve the non-invasive in-situ diagnosis of ALI through in mice, and provides a feasible strategy for early diagnosis and drug therapy of ALI and its complications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Free iron in human serum or non-transferrin-bound iron (NTBI) can generate free radicals and lead to oxidative damage. Moreover, it is highly toxic to various tissues and a vital biomarker related to the iron-loading status of thalassemia and Alzheimer's patients. In NTBI in healthy individuals, NTBI levels are typically less than 1 µM; current NTBI analysis usually requires advanced instrumentation and many-step sample pretreatment. To address this issue, we employed our invented BODIPY derivative, BODIPY-PH, as a fluorescence probe and trapped it onto the microcentrifuge tube lid using tapioca starch. The fluorescence intensity of BODIPY-PH increased with increasing NTBI concentration (turn-on). The developed portable reaction chamber facilitates rapid analysis (∼5 min) using small sample volumes (10 μL sample in a total volume of 600 μL). Under optimum conditions, using the sample-developed portable fluorescence device and fluorescence spectrometer, we achieved impressive limits of detection (LOD) of 0.003 and 0.0015 μM, respectively. Furthermore, the developed sensors show relatively high selectivity toward Fe 3+ over other metal ions and biomolecules (i.e., Fe 2+ , Cr 3+ , Cu 2+ , and glucose). The sensor performance in serum samples of thalassemia patients exhibited no significant difference compared to the labeled value (obtained from standard methods). Overall, the developed fluorescence sensor is suitable for determining NTBI and offers high sensitivity, high selectivity, and a short incubation time (5 min). Moreover, the method requires a limited number of reagents, is simple to use, and uses low-cost equipment to determine NTBI in human serum samples., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

Multidisciplinary therapy centered on radical surgery for resectable pancreatic cancer is expected to prolong prognosis, but relies on CA19-9 biomarker levels to determine treatment strategy. Boron neutron capture therapy (BNCT) is a chemoradiotherapy using tumor hyperaccumulator boron drugs and neutron irradiation. The purpose of this study is to investigate novel boron drug agents for BNCT for pancreatic cancer. Bioinformatics was used to evaluate the uptake of current boron amino acid (BPA) drugs for BNCT into pancreatic cancer. The expression of the amino acid transporter LAT1, a BPA uptake transporter, was low in pancreatic cancer and even lower in high CA19-9 pancreatic cancer. In contrast, the glucose transporter was high in high CA19-9 pancreatic cancers and inversely correlated with LAT1 expression. Considering the low EPR effect in pancreatic cancer, we synthesized a small molecule Glucose-BSH, which is boron BSH bound to glucose, and confirmed its specific uptake in pancreatic cancer. uptake of Glucose-BSH was confirmed in an environment compatible with the tumor microenvironment. The therapeutic efficacy and safety of Glucose-BSH by therapeutic neutron irradiation were confirmed with BNCT. We report Glucose-BSH boron drug discovery study of a Precision Medicine BNCT with application to high CA19-9 pancreatic cancer., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. All of author have no C.O.I., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Alzheimer's disease (AD), gradually recognized as an untreatable neurodegenerative disorder, has been considered to be closely associated with Aβ plaques, which consist of β-amyloid protein (Aβ) and is one of the crucial pathological features of AD. There are no obvious symptoms in the initial phase of AD, and thus the therapeutic interventions are important for early diagnosis of AD. Moreover, recent researches have indicated that lipid droplets might serve as a potential ancillary biomarker, and its viscosity changes are closely associated to the pathological process of AD. Herein, two newly fluorescent probes 5QSZ and BQSZ have been developed and synthesized for identifying Aβ aggregates and detecting the viscosity of lipid droplet. After selectively binding to Aβ aggregates, 5QSZ and BQSZ exhibited linear and obvious fluorescence enhancements (32.58 and 36.70 folds), moderate affinity (K d  = 268.0 and 148.6 nM) and low detection limits (30.11 and 65.37 nM) in aqueous solutions. Further fluorescence staining of 5QSZ on brain tissue sections of APP/PS1 transgenic mouse exhibited the higher selectivity of 5QSZ towards Aβ aggregates locating at the core of the plaques. Furthermore, 5QSZ and BQSZ displayed strong linear fluorescence emission enhancements towards viscosity changes and would be utilized to monitor variation in cellular viscosity induced by LPS or monensin. These two probes were non-cytotoxic and showed good localization in lipid droplets. Therefore, 5QSZ and BQSZ could serve as potential bi-functional fluorescent probes to image Aβ aggregates and monitor the viscosity of lipid droplets, which have significant implications for the early diagnosis and progression of AD., Competing Interests: Declaration of competing interest All authors declare no competing interests. There is no conflict of interest in the submission of this article, and it has been authorized for publication by all authors., (Copyright © 2024 Elsevier B.V. All rights reserved.)