A carrier-free nanovaccine combined with cancer immunotherapy overcomes gemcitabine resistance.

Drug resistance is a significant challenge in cancer chemotherapy and is a primary factor contributing to poor recovery for cancer patients. Although drug-loaded nanoparticles have shown promise in overcoming chemotherapy resistance, they often carry a combination of drugs and require advanced design and manufacturing processes. Furthermore, they seldom approach chemotherapy-resistant tumors from an immunotherapy perspective. In this study, we developed a therapeutic nanovaccine composed solely of chemotherapy-induced resistant tumor antigens (CIRTAs) and the immune adjuvant Toll-like receptor (TLR) 7/8 agonist R848 (CIRTAs@R848). This nanovaccine does not require additional carriers and has a simple production process. It efficiently delivers antigens and immune stimulants to dendritic cells (DCs) simultaneously, promoting DCs maturation. CIRTAs@R848 demonstrated significant tumor suppression, particularly when used in combination with the immune checkpoint blockade (ICB) anti-PD-1 (αPD-1). The combined therapy increased the infiltration of T cells into the tumor while decreasing the proportion of regulatory T cells (Tregs) and modulating the tumor microenvironment, resulting in long-term immune memory. Overall, this study introduces an innovative strategy for treating chemotherapy-resistant tumors from a novel perspective, with potential applications in personalized immunotherapy and precision medicine.

Application of new tetra-cationic imidazolium ionic liquids for capture and conversion of CO2 to amphiphilic calcium carbonate nanoparticles as a green additive in water based drilling fluids.

Conversion and capture of carbon pollutants based on carbon dioxide to valuable green oil-field chemicals are target all over the world for controlling the global warming. The present article used new room temperature amphiphilic imidazolium ionic liquids with superior surface activity in the aqueous solutions to convert carbon dioxide gas to superior amphiphilic calcium carbonate nanoparticles. In this respect, tetra-cationic ionic liquids 2-(4-dodecyldimethylamino) phenyl)-1,3-bis (3-dodecyldimethylammnonio) propyl) bromide-1-H-imidazol-3-ium acetate and 2-(4-hexyldimethylamino) phenyl)-1,3-bis(3-hexcyldimethylammnonio) propyl) bromide-1 H-imidazol-3-ium acetate were prepared. Their chemical structures, thermal as well as their carbon dioxide absorption/ desorption characteristics were evaluated. They were used as solvent and capping agent to synthesize calcium carbonate nanoparticles with controlled crystalline lattice, sizes, thermal properties and spherical surface morphologies. The prepared calcium carbonate nanoparticles were used as additives for the commercial water based drilling mud to improve their filter lose and rheology. The data confirm that the lower concentrations of 2-(4-dodecyldimethylamino) phenyl)-1,3-bis (3-dodecyldimethylammnonio) propyl) bromide-1-H-imidazol-3-ium acetate achieved lower seawater filter lose and improved viscosities.

The dynamin inhibitor, dynasore, prevents zoledronate-induced viability loss in human gingival fibroblasts by partially blocking zoledronate uptake and inhibiting endosomal acidification.

OBJECTIVE: For treatment of medication-related osteonecrosis of the jaw, one proposed approach is the use of a topical agent to block entry of these medications in oral soft tissues. We tested the ability of phosphonoformic acid (PFA), an inhibitor of bisphosphonate entry through certain sodium-dependent phosphate contransporters (SLC20A1, 20A2, 34A1-3) as well as Dynasore, a macropinocytosis inhibitor, for their abilities to prevent zoledronate-induced (ZOL) death in human gingival fibroblasts (HGFs). METHODOLOGY: MTT assay dose-response curves were performed to determine non-cytotoxic levels of both PFA and Dynasore. In the presence of 50 µM ZOL, optimized PFA and Dynasore doses were tested for their ability to restore HGF viability. To determine SLC expression in HGFs, total HGF RNA was subjected to quantitative real-time RT-PCR. Confocal fluorescence microscopy was employed to see if Dynasore inhibited macropinocytotic HGF entry of AF647-ZOL. Endosomal acidification in the presence of Dynasore was measured by live cell imaging utilizing LysoSensor Green DND-189. As a further test of Dynasore's ability to interfere with ZOL-containing endosomal maturation, perinuclear localization of mature endosomes containing AF647-ZOL or TRITC-dextran as a control were assessed via confocal fluorescence microscopy with CellProfiler™ software analysis of the resulting photomicrographs. RESULTS: 0.5 mM PFA did not rescue HGFs from ZOL-induced viability loss at 72 hours while 10 and 30 µM geranylgeraniol did partially rescue. HGFs did not express the SLC transporters as compared to the expression in positive control tissues. 10 µM Dynasore completely prevented ZOL-induced viability loss. In the presence of Dynasore, AF647-ZOL and FITC-dextran co-localized in endosomes. Endosomal acidification was inhibited by Dynasore and perinuclear localization of both TRITC-dextran- and AF647-ZOL-containing endosomes was inhibited by 30 µM Dynasore. CONCLUSION: Dynasore prevents ZOL-induced viability loss in HGFs by partially interfering with macropinocytosis and by inhibiting the endosomal maturation pathway thought to be needed for ZOL delivery to the cytoplasm.

Prolonged Skin Retention of Luliconazole from SLNs Based Topical Gel Formulation Contributing to Ameliorated Antifungal Activity.

The development of effective therapy is necessary because the patients have to contend with long-term therapy as skin fungal infections usually relapse and are hardly treated. Despite being a potent antifungal agent, luliconazole (LCZ) has certain shortcomings such as limited skin penetration, low solubility in aqueous medium, and poor skin retention. Solid Lipid Nanoparticles (SLNs) were developed using biodegradable lipids by solvent injection method and were embodied into the gel base for topical administration. After in-vitro characterizations of the formulations, molecular interactions of the drug with excipients were analyzed using in-silico studies. Ex-vivo release was determined in contrast to the pure LCZ and the commercial formulation followed by in-vivo skin localization, skin irritation index, and antifungal activity. The prepared SLNs have an average particle size of 290.7 nm with no aggregation of particles and homogenous gels containing SLNs with ideal rheology and smooth texture properties were successfully prepared. The ex-vivo LCZ release from the SLN gel was lower than the commercial formulation whereas its skin deposition and skin retention were higher as accessed by CLSM studies. The drug reaching the systemic circulation and the skin irritation potential were found to be negligible. The solubility and drug retention in the skin were both enhanced by the development of SLNs as a carrier. Thus, SLNs offer significant advantages by delivering long lasting concentrations of LCZ at the site of infection for a complete cure of the fungal load together with skin localization of the topical antifungal drug.

Letter to Editor, "The effects of dabrafenib and/or trametinib treatment in Braf V600mutant glioma: a systematic review and metaanalysis".

This systematic review and meta-analysis evaluates the effects of dabrafenib and/or trametinib in treating BRAF V600-mutant gliomas. The study analyzed eight trials involving both high-grade and low-grade glioma patients, assessing outcomes such as progression-free survival (PFS), overall survival (OS), adverse events (AEs), and disease response. The pooled results showed a median PFS of 6.10 months and OS of 22.73 months, with notable improvement in disease response rates when using combination therapy. However, the high incidence of AEs (50%) and death events (43%) necessitates caution in interpreting these results. The study's limitations include a lack of randomized controlled trials and high heterogeneity in AE data. Future research should focus on larger, controlled studies, standardized AE assessments, and exploration of neurocognitive outcomes to better understand and optimize treatment strategies for BRAF V600-mutant gliomas.

A difunctional NMR&CD probe for specific detection and enantiomeric recognition of biothiols in complex mixtures.

BACKGROUND: Biothiols are important for numerous cellular processes, such as resisting oxidative stress and protecting cell health. Their abnormal levels and molecular configurations have been associated with various diseases. So, establishing an effective and reliable method for the specific detection and enantiomeric discrimination of diverse biothiols is highly meaningful. RESULTS: We have developed a new NMR and CD probe using 1,4-dinitroimidazole, specifically targeting the thiol group. This probe allows for the specific detection and enantiomeric recognition of biothiols in complex mixtures. We achieved this by identifying the distinguishable 1H NMR signals of 2nd in imidazole-ring of the resulting 4NI-biothiols in the downfield region at 7-8 ppm and newly discovered induced CD signals within 290-430 nm. Using this probe, the limits of detection of Cys, GSH, and Hcy, the recovery rates, and the concentration of GSH extracted from HEK293T cells were determined by measuring the unique downfield 1H NMR signals. Moreover, Cys, GSH, and Hcy can be discriminated simultaneously in complicated samples at a pH range of 2-3.5. Furthermore, this probe can also be utilized to sense chiral thiol-drugs. SIGNIFICANCE: This method offers a cost-effective and accurate sensing solution for the specific detection of biothiols in complex mixtures, with stereochemical recognition.

Preclinical evaluation of avutometinib and defactinib in high-grade endometrioid endometrial cancer.

BACKGROUND: High-grade endometrial cancers (EAC) are aggressive tumors with a high risk of progression after treatment. As EAC may harbor mutations in the RAS/MAPK pathways, we evaluated the preclinical in vitro and in vivo efficacy of avutometinib, a RAF/MEK clamp, in combination with the focal adhesion kinase (FAK) inhibitors defactinib or VS-4718, against multiple primary EAC cell lines and xenografts. METHODS: Whole-exome sequencing (WES) was used to evaluate the genetic landscape of five primary EAC cell lines. The in vitro activity of avutometinib and defactinib as single agents and in combination was evaluated using cell viability, cell cycle, and cytotoxicity assays. Mechanistic studies were performed using Western blot assays while in vivo experiments were completed in UTE10 engrafted mice treated with either vehicle, avutometinib, VS-4718, or their combination through oral gavage. RESULTS: WES results demonstrated multiple EAC cell lines to harbor genetic derangements in the RAS/MAPK pathway including KRAS/PTEN/PIK3CA/BRAF/ARID1A, potentially sensitizing to FAK and RAF/MEK inhibition. Five out of five of the EAC cell lines demonstrated in vitro sensitivity to FAK and/or RAF/MEK inhibition. By Western blot assays, exposure of EAC cell lines to defactinib, avutometinib, and their combination demonstrated decreased phosphorylated FAK (p-FAK) as well as decreased p-MEK and p-ERK. In vivo the combination of avutometinib/VS-4718 demonstrated superior tumor growth inhibition compared to single-agent treatment and controls starting at Day 9 (p < 0.02 and p < 0.04) in UTE10 xenografts. CONCLUSIONS: Avutometinib, defactinib, and to a larger extent their combinations, demonstrated promising in vitro and in vivo activity against EAC cell lines and xenografts. These preclinical data support the potential clinical evaluation of this combination in high-grade EAC patients.

Sorption and degradation processes of imidacloprid in Florida soils.

Imidacloprid (IDP) is an active ingredient of the Admire brand pesticide used to control the vector (Asian citrus psyllid) that transmits the causative organism Candidatus Liberibacter asiaticus (CLas) for citrus greening or huanglongbing disease. Imidacloprid products are applied via soil drench where citrus roots are mostly concentrated which is between 0 and 60 cm depth. These soil depths exhibit different characteristics that may affect IDP leaching beyond the rooting zone. Representative soil samples were collected from Entisols and Ultisols, which are the dominant soil orders under citrus production in central Florida, at 15 cm increments up to 60 cm to estimate and understand the batch sorption, kinetics, equilibria, and degradation of IDP. Results showed that the equilibrium time for IDP at 0-15 cm depth (10 hours) was 2 times faster than at 15-60 cm (20 hours) for the Entisol. Nevertheless, all depths reached equilibrium within 24 hours for the Entisol. The 0-30 cm depth adsorbed 2 times more IDP than the 30-60 cm depth for both soils. Nevertheless, the adsorption coefficient was approximately ≤ 1 mL g-1 for both soils. The half-life of IDP in both soils ranged from 10 to 17 days. The Entisol showed higher adsorption than the Ultisol at both depths, probably due to relatively lower organic carbon (OC) content in the Ultisol compared to the Entisol. Thus, the Ultisol showed high IDP leaching vulnerability compared to the Entisol. Movement of IDP is affected by the amount of OC in the citrus critical zone.

Design, synthesis, and biological evaluation of imidazolylacetophenone oxime derivatives as novel brain-penetrant agents for Alzheimer's disease treatment.

Alzheimer's disease (AD, also known as dementia) has become a serious global health problem along with population aging, and neuroinflammation is the underlying cause of cognitive impairment in the brain. Nowadays, the development of multitarget anti-AD drugs is considered to be one effective approach. Imidazolylacetophenone oxime ethers or esters (IOEs) were multifunctional agents with neuroinflammation inhibition, metal chelation, antioxidant and neuroprotection properties against Alzheimer's disease. In this study, IOEs derivatives 1-8 were obtained by structural modifications of the oxime and imidazole groups, and the SARs showed that (Z)-oxime ether (derivative 2) had stronger anti-neuroinflammatory and neuroprotective ability than (E)-congener. Then, IOEs derivatives 9-30 were synthesized based on target-directed ligands and activity-based groups hybridization strategy. In vitro anti-AD activity screening revealed that some derivatives exhibited potentially multifunctional effects, among which derivative 28 exhibited the strongest inhibitory activity on NO production with EC50 value of 0.49 µM, and had neuroprotective effects on 6-OHDA-induced cell damage and RSL3-induced ferroptosis. The anti-neuroinflammatory mechanism showed that 28 could inhibit the release of pro-inflammatory factors PGE2 and TNF-α, down-regulate the expression of iNOS and COX-2 proteins, and promote the polarization of BV-2 cells from pro-inflammatory M1 phenotype to anti-inflammatory M2 phenotype. In addition, 28 can dose-dependently inhibit acetylcholinesterase (AChE) and Aß42 aggregation. Moreover, the selected nuclide [18F]-labeled 28 was synthesized to explore its biodistribution by micro-PET/CT, of which 28 can penetrate the blood-brain barrier (BBB). These results shed light on the potential of 28 as a new multifunctional candidate for AD treatment.

Efficacy and safety evaluation of imidafenacin administered twice daily for continency recovery following radical prostatectomy in prostate cancer patients: Prospective open-label case-controlled randomized trial.

PURPOSE: This study aims to prospectively analyze the effects of anticholinergic therapy using imidafenacin on detrusor overactivity occurring after robot-assisted radical prostatectomy (RARP). MATERIALS AND METHODS: Patients were followed-up at outpatient visits 2-4 weeks post-surgery (visit 2) to confirm the presence of urinary incontinence. Those confirmed with urinary incontinence were randomly assigned in a 1:1 ratio to the anticholinergic medication group (imidafenacin 0.1 mg twice daily) or the control group. Patients were followed-up at 1, 3, and 6 months post-surgery for observational assessments, including the International Prostate Symptom Score (IPSS) and Overactive Bladder Symptom Score (OABSS). RESULTS: A total of 49 patients (25 in the treatment group and 24 in the control group) were randomized for the study. There were no differences observed between the groups in terms of age, comorbidities, prostate size, or pathological staging. According to the IPSS questionnaire results, there was no statistically significant difference between the medication and control groups (p=0.161). However, when comparing storage and voiding symptoms separately, there was a statistically significant improvement in storage symptom scores (p=0.012). OABSS also revealed statistically significant improvement in symptoms from 3 months post-surgery (p=0.005), which persisted until 6 months post-surgery (IPSS storage: p=0.023, OABSS: p=0.013). CONCLUSIONS: In the case of urinary incontinence that occurs after RARP, even if the function of the intrinsic sphincter is sufficiently preserved, if urinary incontinence persists due to changes in the bladder, pharmacological therapy using imidafenacin can be beneficial in managing urinary incontinence.

Cataract Formation in a Child Receiving Dabrafenib and Trametinib Therapy.

The authors report a case of bilateral cataract in a 9-year-old girl after being treated with a combination of the targeted therapy drugs dabrafenib and trametinib. Although adverse effects have been reported with this treatment, this report is the first documented case of cataract as a complication. [J Pediatr Ophthalmol Strabismus. 2024;61(5):e47-e49.].

Letter to editor: The efects of dabrafenib and/or trametinib treatment in Braf V600­mutant glioma: a systematic review and meta-analysis.

The systematic review and meta-analysis titled "The Effects of Dabrafenib and/or Trametinib Treatment in BRAF V600-Mutant Glioma" provides a critical evaluation of these targeted therapies for a challenging subset of gliomas. This review is notable for its comprehensive data integration, offering a robust assessment of the efficacy and safety of dabrafenib and trametinib. By focusing on BRAF V600 mutations, it contributes valuable insights into personalized treatment strategies. However, limitations include study heterogeneity and a lack of long-term follow-up data, which hinder the generalizability and complete understanding of treatment effects. Additionally, while the review emphasizes therapeutic potential, it requires a thorough evaluation of adverse effects. Future research should address these limitations by providing more consistent data, longer follow-up, and a balanced view of treatment risks and benefits.

Endocytosis of Synaptic Vesicle in Motor Nerve Endings of FUS Transgenic Mice with a Model of Amyotrophic Lateral Sclerosis.

In experiments on the motor nerve endings of the diaphragm of transgenic FUS mice with a model of amyotrophic lateral sclerosis at the pre-symptomatic stage of the disease, the processes of transmitter release and endocytosis of synaptic vesicles were studied. In FUS mice, the intensity of transmitter release during high-frequency stimulation of the motor nerve (50 imp/sec) was lowered. At the same duration of stimulation, the loading of fluorescent dye FM1-43 was lower in FUS mice. However, at the time of stimulation, during which an equal number of quanta are released in wild-type and FUS mice, no differences in the intensity of dye loading were found. Thus, endocytosis is not the key factor in the mechanism of synaptic dysfunction in FUS mice at the pre-symptomatic stage.

FDA-approved antivirals ledipasvir and daclatasvir downregulate the Src-EPHA2-Akt oncogenic pathway in colorectal and triple-negative breast cancer cells.

Direct-acting antivirals ledipasvir (LDV) and daclatasvir (DCV) are widely used as part of combination therapies to treat Hepatitis C infections. Here we show that these compounds inhibit the proliferation, invasion, and colony formation of triple-negative MDA-MB-231 breast cancer cells, SRC-transduced SW620 colon cancer cells and SRC- transduced NIH3T3 fibroblasts. DCV also inhibits the expression of PDL-1, which is responsible for resistance to immunotherapy in breast cancer cells. The demonstrated low toxicity in many Hepatitis C patients suggests LDV and DCV could be used in combination therapies for cancer patients. At the molecular level, these direct-acting antivirals inhibit the phosphorylation of Akt and the ephrin type A receptor 2 (EPHA2) by destabilizing a Src-EPHA2 complex, although they do not affect the general kinase activity of Src. Thus, LDV and DCV could be effective drugs for Src-associated cancers without the inherent toxicity of classical Src inhibitors.

3D structure of acetolactate synthase explains why the Asp-376-Glu point mutation does not give the same resistance level to different imidazolinone herbicides.

Resistance to ALS-inhibiting herbicides has dramatically increased worldwide due to the persisting evolution of target site mutations that reduce the affinity between the herbicide and the target. We evaluated the effect of the well-known ALS Asp-376-Glu target site mutation on different imidazolinone herbicides, including imazamox and imazethapyr. Greenhouse dose response experiments indicate that the Amaranthus retroflexus biotype carrying Asp-376-Glu was fully controlled by applying the field recommended dose of imazamox, whereas it displayed high level of resistance to imazethapyr. Likewise, Sorghum halepense, carrying Asp-376-Glu showed resistance to field recommended doses of imazethapyr but not of imazamox. Biochemical inhibition and kinetic characterization of the Asp-376-Glu mutant enzyme heterologously expressed using different plant sequence backbones, indicate that the Asp-376-Glu shows high level of insensitivity to imazethapyr but not to imazamox, corroborating the greenhouse results. Docking simulations revealed that imazamox can still inhibit the Asp-376-Glu mutant enzyme through a chalcogen interaction between the oxygen of the ligand and the sulfur atom of the ALS Met200, while imazethapyr does not create such interaction. These results explain the different sensitivity of the Asp-376-Glu mutation towards imidazolinone herbicides, thus providing novel information that can be exploited for defining stewardship guidelines to manage fields infested by weeds harboring the Asp-376-Glu mutation.

Effects of imidazole derivatives on cellular proliferation and apoptosis in myeloid leukemia.

BACKGROUND: Acute promyelocytic leukemia (APL) is the sub-type of Acute myeloid leukemia (AML) which is described by differentiation block at promyelocytic stage and t(15; 17) translocation with All trans retinoic acid (ATRA) and arsenic trioxide (ATO) as standard treatments. Chronic myeloid leukemia (CML) translocation t (19; 22) causes a rise in granulocytes and their immature precursors in the blood. Different mutations cause resistance to first-line tyrosine kinase therapies in CML. Beside drug resistance, leukemia stem cells (LSC) are critical resources for relapse and resistance in APL and CML. The drug toxicity and resistant profile associated with LSC and current therapeutics of APL and CML necessitate the development of new therapies. Imidazoles are heterocyclic nitrogen compounds with diverse cellular actions. The purpose of this research was to assess the anti-leukemic properties of four novel imidazole derivatives including L-4, L-7, R-35, and R-NIM04. METHODS AND RESULTS: Pharmacological and biochemical approaches were used which showed that all four imidazole derivatives interfere with the NB4 cells proliferation, an APL cell line, while only L-7 exhibit anti-proliferative activity against K562 cells, a CML cell line. The anti-proliferative effect of imidazole derivatives was linked to apoptosis induction. Further real-time polymerase chain reaction (RT-PCR) analysis revealed downregulation of AXL-Receptor Tyrosine Kinase (AXL-RTK) and target genes of Wnt/beta-catenin pathway like c-Myc, Axin2 and EYA3. An additive effect was observed after combinatorial treatment of L-7 with standard drugs ATRA or Imatinib on the proliferation of NB4 and K562 cells respectively which was related to further downregulation of target genes of Wnt/beta catenin pathway. CONCLUSION: Imidazole derivatives significantly reduce proliferation of NB4 and K562 cells by inducing apoptosis, down regulating of AXL-RTK and Wnt/ß-catenin target genes.

A metal-organic nanoframework for efficient colorectal cancer immunotherapy by the cGAS-STING pathway activation and immune checkpoint blockade.

Immunotherapy has shown marked progress in promoting systemic anti-colorectal cancer (CRC) clinical effects. For further effectively sensitizing CRC to immunotherapy, we have engineered a pH-sensitive zeolitic imidazolate framework-8 (CS/NPs), capable of efficient cGAS-STING pathway activation and immune checkpoint blockade, by encapsulating the chemotherapeutic mitoxantrone (MTX) and immunomodulator thymus pentapeptide (TP5) and tailoring with tumor-targeting chondroitin sulfate (CS). In this nanoframework, CS endows CS/NPs with specific tumor-targeting activity and reduced systemic toxicity. Of note, the coordinated Zn2+ disrupts glycolytic processes and downregulates the expression of glucose transporter type 1 (GLUT1), thus depriving the cancer cells of their energy. Zn2+ further initiates the adenosine 5'-monophosphate activated protein kinase (AMPK) pathway, which leads to PD-L1 protein degradation and sensitizes CRC cells to immunotherapy. Moreover, the damaged double-stranded DNA during MTX treatment activates the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway, which works together with TP5 induced the proliferation and differentiation of T lymphocytes and dendritic cells to further enhance the anti-CRC immune response. Therefore, CS/NPs efficiently sensitize cells to chemotherapy and stimulate systemic antitumor immune responses both in vitro and in vivo, representing a promising strategy to increase the feasibility of CRC immunotherapy.

[Sartan-induced enteropathy]. / Entéropathie induite par les sartans.

Olmesartan-induced enteropathy was first described twelve years ago. Clinically it is characterized by diarrhea, weight loss and malabsorption. Histological analysis may show duodenal villous atrophy and/or epithelial lymphocytosis (duodenal/colic). Celiac-specific antibodies are negative and gluten avoidance does not improve the symptomatology. This adverse event can occur months or years after the introduction of the causative drug, making it a real diagnostic challenge. The treatment is the avoidance of olmesartan, which will lead to both clinical and histological improvement.

L'entéropathie induite par l'olmésartan est une entité connue depuis une dizaine d'années et se caractérise par un syndrome de malabsorption avec diarrhées et perte pondérale. L'analyse histologique peut montrer une atrophie villositaire duodénale et/ou une lymphocytose épithéliale (duodénale et colique). Les anticorps spécifiques de la maladie cœliaque sont négatifs et l'éviction du gluten n'améliore en rien la symptomatologie. Cet effet indésirable peut se manifester des mois voire des années après l'introduction du traitement, ce qui en fait un réel défi diagnostique. Le traitement est l'éviction de la molécule, accompagnée d'une amélioration tant sur le plan clinique qu'histologique.

An imidazole-copper(I) metallacycle complex exhibiting thermochromic fluorescence.

In this paper, we firstly report the synthesis and structural characterization of a discrete coordination metallacycle complex, [CuI (bipy)]2 (1). The x-ray diffraction structure, temperature-dependent electronic absorption, and photoluminescence spectra have been investigated. The solid-state fluorescence at variable temperatures shows that complex 1 exhibits an obvious thermochromic fluorescence. At low temperature, the dual fluorescence with peaks at 590 and 694 nm was observed. The emission color significantly changes from red at 77 K to yellow at 200 K and blue-green at 330 K. The thermochromic fluorescent molecular materials show great potential as temperature sensing.

One-Pot Synthesis of a pH-Sensitive MOF Integrated with Glucose Oxidase for Amplified Tumor Photodynamic/Photothermal Therapy.

Photothermal therapy (PTT) and photodynamic therapy (PDT) provide targeted approaches to cancer treatment, but each therapy has inherent limitations such as insufficient tissue penetration, uneven heat distribution, extreme hypoxia, and overexpressed HSP90 in tumor cells. To address these issues, herein, by encapsulating the IR780 dye and glucose oxidase (GOx) enzyme within ZIF-8 nanoparticles, we created a versatile system capable of combining photodynamic and enhanced photothermal therapy. The integration of the IR780 dye facilitated the generation of reactive oxygen species and hyperthermia upon light activation, enabling dual-mode cancer cell ablation. Moreover, GOx catalyzes the decomposition of glucose into gluconic acid and hydrogen peroxide, leading to the inhibition of ATP production and downregulation of heat shock protein 90 (HSP90) expression, sensitizing cancer cells to heat-induced cytotoxicity. This synergistic combination resulted in significantly improved therapeutic outcomes. Both in vitro and in vivo results validated that the nanoplatform demonstrated superior specificity and favorable therapeutic responses. Our innovative approach represents a promising strategy for overcoming current limitations in cancer treatments and offers the potential for clinical translation in the future.