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Herein, we report on highly Ba2+ selective fluorescence sensing in water by a fluorescent probe consisting of a benzo‐21‐crown‐7 as a Ba2+ binding unit (ionophore) and a tetramethylated BODIPY fluorophore as a fluorescence reporter. This fluorescent probe showed a Ba2+ induced fluorescence enhancement (FE) by a factor of 12±1 independently of the pH value and a high Ba2+ sensitivity with a limit of detection (LOD) of (17.2±0.3) μM. Moreover, a second fluorescent probe consisting of the same BODIPY fluorophore, but a benzo‐18‐crown‐6 as a cation‐responsive binding moiety, showed an even higher FE upon Ba2+ complexation by a factor of 85±3 and a lower LOD of (13±3) μM albeit a lower Ba2+ selectivity. The fluorescence sensing mechanism of Ba2+ was further investigated by time‐resolved fluorescence as well as transient absorption spectroscopy (TAS) and it turned out that within these probes a blocking of a photoinduced electron transfer (PET) by Ba2+ is very likely responsible for the FE. [ABSTRACT FROM AUTHOR]

Herein, we report on fluorescent probes which enable the selective quantification of Na+ and K+ in water by fluorescence enhancement (FE) independent of the pH value. These fluorescent probes, so called fluoroionophores, consist of benzo‐crown‐ether derivatives as ionophores, a benzo‐15‐crown‐5 (cf. 5) or a benzo‐18‐crown‐6 (cf. 6), respectively, to selectively bind either Na+ or K+ and a 4,4‐difluoro‐1,3,5,7‐tetramethyl‐4‐bora‐3a,4a‐diaza‐s‐indacene (BODIPY) fluorophore. The fluoroionophore 5 shows a FE factor of 7.3 in the presence of 1000 mM Na+ and 6 of 4.7 upon addition of 250 mM K+ in an acidic environment. The dissociation constants (Kd) for 5+Na+ is 276 mM and for 6+K+ is 18 mM enabling the fluorometric determination of biological relevant Na+ or K+ levels. The fluorescence intensities of 5 and 6 were not impacted over a broad range of proton concentrations (pH stable from 3.5 to 9.5) and by the presence of other biologically relevant cations. [ABSTRACT FROM AUTHOR]

Herein, we represent cation‐responsive fluorescent probes for the divalent cations Zn2+, Mg2+ and Ca2+, which show cation‐induced fluorescence enhancements (FE) in water. The Zn2+‐responsive probes Zn1, Zn2, Zn3 and Zn4 are based on o‐aminoanisole‐N,N‐diacetic acid (AADA) derivatives and show in the presence of Zn2+ FE factors of 11.4, 13.9, 6.1 and 8.2, respectively. Most of all, Zn1 and Zn2 show higher Zn2+ induced FE than the regioisomeric triazole linked fluorescent probes Zn3 and Zn4, respectively. In this set, ZN2 is the most suitable probe to detect extracellular Zn2+ levels. For the Mg2+‐responsive fluorescent probes Mg1, Mg2 and Mg3 based on o‐aminophenol‐N,N,O‐triacetic acid (APTRA) derivatives, we also found that the regioisomeric linkage influences the fluorescence responds towards Mg2+ (Mg1+100 mM Mg2+ (FEF=13.2) and Mg3+100 mM Mg2+ (FEF=2.1)). Mg2 shows the highest Mg2+‐induced FE by a factor of 25.7 and an appropriate Kd value of 3 mM to measure intracellular Mg2+ levels. Further, the Ca2+‐responsive fluorescent probes Ca1 and Ca2 equipped with a 1,2‐bis(o‐aminophenoxy)ethane‐N,N,N',N'‐tetraacetic acid (BAPTA) derivative show high Ca2+‐induced FEs (Ca1 (FEF=22.1) and Ca2 (FEF=23.0)). Herein, only Ca1 (Kd=313 nM) is a suitable Ca2+ fluorescent indicator to determine intracellular Ca2+ levels. [ABSTRACT FROM AUTHOR]

Simple Summary: Although multiple meta-analyses on active specific immunotherapy treatment for glioblastoma multiforme (GBM) have demonstrated a significant prolongation of overall survival, no single research group has succeeded in demonstrating the efficacy of this type of treatment in a prospective, double-blind, placebo-controlled, randomized clinical trial. In this paper, we explain how the complexity of the tumor biology and tumor–host interactions make proper stratification of a control group impossible. The individualized characteristics of advanced therapy medicinal products for immunotherapy contribute to heterogeneity within an experimental group. The dynamics of each tumor and in each patient aggravate comparative stable patient groups. Finally, combinations of immunotherapy strategies should be integrated with first-line treatment. We illustrate the complexity of a combined first-line treatment with individualized multimodal immunotherapy in a group of 70 adults with GBM and demonstrate that the integration of immunogenic cell death treatment within maintenance chemotherapy followed by dendritic cell vaccines and maintenance immunotherapy might provide a step towards improving the overall survival rate of GBM patients. Immunotherapies represent a promising strategy for glioblastoma multiforme (GBM) treatment. Different immunotherapies include the use of checkpoint inhibitors, adoptive cell therapies such as chimeric antigen receptor (CAR) T cells, and vaccines such as dendritic cell vaccines. Antibodies have also been used as toxin or radioactive particle delivery vehicles to eliminate target cells in the treatment of GBM. Oncolytic viral therapy and other immunogenic cell death-inducing treatments bridge the antitumor strategy with immunization and installation of immune control over the disease. These strategies should be included in the standard treatment protocol for GBM. Some immunotherapies are individualized in terms of the medicinal product, the immune target, and the immune tumor–host contact. Current individualized immunotherapy strategies focus on combinations of approaches. Standardization appears to be impossible in the face of complex controlled trial designs. To define appropriate control groups, stratification according to the Recursive Partitioning Analysis classification, MGMT promotor methylation, epigenetic GBM sub-typing, tumor microenvironment, systemic immune functioning before and after radiochemotherapy, and the need for/type of symptom-relieving drugs is required. Moreover, maintenance of a fixed treatment protocol for a dynamic, deadly cancer disease in a permanently changing tumor–host immune context might be inappropriate. This complexity is illustrated using our own data on individualized multimodal immunotherapies for GBM. Individualized medicines, including multimodal immunotherapies, are a rational and optimal yet also flexible approach to induce long-term tumor control. However, innovative methods are needed to assess the efficacy of complex individualized treatments and implement them more quickly into the general health system. [ABSTRACT FROM AUTHOR]

Herein, we report the synthesis and sensing characteristics of 4,4'-methoxy-substituted BODIPY fluorescent probes (OBODIPYs) 3, 4 and 5 equipped with differently sized benzo-crown ethers (cf. Scheme 1, 3 (benzo-15-crown-5), 4 (benzo-18-crown-6) and 5 (benzo-21-crown7)). O-BODIPYs 3, 4 and 5 exhibited in comparison to their known F-BODIPY analogues 3a, 4a and 5a (cf. Scheme 1) an improved solubility in aqueous medium and higher fluorescence quantum yields. Fluorometric study in aqueous solutions of 3, 4 and 5 in the presence of different cations show cation induced fluorescence enhancements (FE). Compared to the benzo-crown ether substituted F-BODIPY analogues 3a, 4a and 5a, we found for the free O-BODIPYs 3, 4 and 5 higher fluorescence quantum yields (ϕf ) but lower cation induced FEs. We show that in aqueous medium the fluorescence quenching process (OFF switching), a photoinduced electron transfer, in O-BODIPYs 3, 4 and 5 is less effective and consequently sensitive and selective ON switching of the fluorescence by cations, too. Albeit these observations the novel benzo-21-crown-7 equipped fluorescent probe 5 exhibits a good fluorometric Ba2+ selectivity and Ba2+ sensitivity in conjunction to their superior aqueous solubility., (© 2024 Wiley‐VCH GmbH.)

Glioblastoma (GBM) remains an orphan cancer disease with poor outcome. Novel treatment strategies are needed. Immunotherapy has several modes of action. The addition of active specific immunotherapy with dendritic cell vaccines resulted in improved overall survival of patients. Integration of DC vaccination within the first-line combined treatment became a challenge, and immunogenic cell death immunotherapy during chemotherapy was introduced. We used a retrospective analysis using real world data to evaluate the complex combined treatment, which included individualized multimodal immunotherapy during and after standard of care, and which required adaptations during treatment, and found a further improvement of overall survival. We also discuss the use of real world data as evidence. Novel strategies to move the field of individualized multimodal immunotherapy forward for GBM patients are reviewed., (Copyright © 2024 Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

Herein, we report on highly Ba 2+ selective fluorescence sensing in water by a fluorescent probe consisting of a benzo-21-crown-7 as a Ba 2+ binding unit (ionophore) and a tetramethylated BODIPY fluorophore as a fluorescence reporter. This fluorescent probe showed a Ba 2+ induced fluorescence enhancement (FE) by a factor of 12±1 independently of the pH value and a high Ba 2+ sensitivity with a limit of detection (LOD) of (17.2±0.3) μM. Moreover, a second fluorescent probe consisting of the same BODIPY fluorophore, but a benzo-18-crown-6 as a cation-responsive binding moiety, showed an even higher FE upon Ba 2+ complexation by a factor of 85±3 and a lower LOD of (13±3) μM albeit a lower Ba 2+ selectivity. The fluorescence sensing mechanism of Ba 2+ was further investigated by time-resolved fluorescence as well as transient absorption spectroscopy (TAS) and it turned out that within these probes a blocking of a photoinduced electron transfer (PET) by Ba 2+ is very likely responsible for the FE., (© 2023 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)