Partially Bio-Based Benzoxazine Monomers Derived from Thymol: Photoluminescent Properties, Polymerization Characteristics, Hydrophobic Coating Investigations, and Anticorrosion Studies.

In this work, four thymol-based benzoxazines were synthesized using four primary amines with different chain lengths, namely methylamine, ethylamine, 1-propylamine, and 1-butylamine, which are then named T-m, T-e, T-p, and T-b, respectively. The optical properties of the synthesized thymol-based benzoxazines were examined via the photoluminescent study of their solutions in acetone. The results show that all the prepared benzoxazines emitted blue light with the maximum wavelengths from 425 to 450 nm when irradiated by the excitation wavelengths from 275 to 315 nm. The maximum excitation wavelengths are found to be 275 nm. The polymerization of the thymol-based benzoxazines is triggered by heat treatments with different conditions (160, 180, and 200 °C for 1 h). According to the FTIR results, the heat-curing process introduces a presence of the OH peak, of which intensity increases as the curing temperature increases. Thermal decompositions of thymol-based benzoxazines regarding TGA analyses reveal the enhancement of thermal stability of the benzoxazines with respect to the N-substituent chain length, as significantly observed the change in the first thermal decomposition at temperature ranged from 253 to 260 °C. Synthesized benzoxazine derivatives are further employed to coat the substrate, e.g., the glass slides. The investigation of the water contact angle shows that the coating of the benzoxazines onto the surface improves the hydrophobicity of the substrate, resulting in the enlargement of the contact angle from 25.5° to 93.3°. Moreover, the anticorrosion performance of the polybenzoxazine coatings is examined using potentiodynamic polarization techniques. The results illustrate the anticorrosion efficiency of the thymol-based polybenzoxazine up to 99.99%. Both hydrophobic and electrochemical studies suggest the feasibility for employing benzoxazines in anticorrosion coating applications.

Quantifying non-transferrin-bound iron (NTBI) in human plasma: incorporating BODIPY-pyridylhydrazone (BODIPY-PH) within a thin green film linked to a portable fluorescence-based device.

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 Fe3+ over other metal ions and biomolecules (i.e., Fe2+, Cr3+, Cu2+, 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.

Addressing Water Contamination and Associated Health Issues through Community-Based Interventions: A Case Study in Khon Kaen Province.

A recent study conducted in Khon Kaen Province, Thailand, evaluated the effectiveness of a technology-assisted intervention aimed at improving water quality and addressing related health issues in communities around key water bodies. The intervention targeted health concerns associated with water contamination, including chronic kidney diseases, skin conditions, hypertension, and neurological symptoms. The study included water quality assessments and health evaluations of 586 residents and implemented a Learning Innovation Platform (LIP) across 13 communities. Results showed significant improvements in the community, including a decrease in hypertension and skin-related health issues, as well as enhanced community awareness and proficiency in implementing simple water quality assessments and treatment. The study demonstrated the value of a comprehensive, technology-driven community approach, effectively enhancing water quality and health outcomes, and promoting greater community awareness and self-sufficiency in managing environmental health risks.

Cannabidiol and Aza-BODIPY Coencapsulation for Photodynamic Therapy Enhancement in Liver Cancer Cells.

Photodynamic therapy (PDT) and cannabidiol (CBD) have been explored for their potential in synergistic cancer treatment. In this study, we employed CBD oil as a lipid phase, encapsulated within AZB-I@Lec-T to create lipid-based nanoparticles. Here, CBD oil does two tasks: it acts as a pyroptosis agent to destroy liver cancer cells and as a lipid phase to dissolve the photosensitizer. It was expected that this system would offer synergistic therapy between CBD and PDT better than a single use of each treatment. With a series of in vitro experiments, the nanoparticles exhibited induced apoptosis in 68% of HepG2 cells treated with AZB-I@Lec-T@CBD and near-infrared (NIR)-light irradiation, reducing expression levels of antioxidant defense system genes. Furthermore, both components worked well in a submicromolar range when combined in our formulation. These results highlight the potential for amplifying primary cellular damage with the combination of PDT and CBD encapsulation, providing a promising therapeutic approach for liver cancer treatment guidelines.

Development of a new series of thioacetal based fluorescence chemosensors for highly sensitive determination of Hg2+ in environmental samples and cell imaging.

Mercury ion is one of the most harmful metal ions with significant hazards to the environment and human health. Thus, the development of innovative, sensitive, and selective sensors to help address the detrimental impacts of heavy metal contamination is necessary. In this work, we present three new chemosensors based on the deprotection reaction of the thioacetal group for distinguishing Hg2+ in environmental samples. These chemosensors show good photophysical properties with high quantum yield in aqueous medium. These prepared chemosensors were employed as fluorometric sensors for the determination of Hg2+ through the quenching of fluorescence emission due to the Hg2+-induced hydrolysis of the thioacetal to the aldehyde group. In the presence of Hg2+, chemosensors showed an emissive color transformation from blue fluorescence to non-fluorescence under UV light, which was readily seen by the visual eye. These chemosensors also exhibited highly distinctive selectivity toward Hg2+ over other interfering metal ions, with detection limits of 1.1 ppb, 13.4 ppb, and 12.7 ppb. Moreover, the practical applicability of chemosensor was successfully demonstrated in real water samples and herb extract samples.

Enhancing Glucose Biosensing with Graphene Oxide and Ferrocene-Modified Linear Poly(ethylenimine).

We designed and optimized a glucose biosensor system based on a screen-printed electrode modified with the NAD-GDH enzyme. To enhance the electroactive surface area and improve the electron transfer efficiency, we introduced graphene oxide (GO) and ferrocene-modified linear poly(ethylenimine) (LPEI-Fc) onto the biosensor surface. This strategic modification exploits the electrostatic interaction between graphene oxide, which possesses a negative charge, and LPEI-Fc, which is positively charged. This interaction results in increased catalytic current during glucose oxidation and helps improve the overall glucose detection sensitivity by amperometry. We integrated the developed glucose sensor into a flow injection (FI) system. This integration facilitates a swift and reproducible detection of glucose, and it also mitigates the risk of contamination during the analyses. The incorporation of an FI system improves the efficiency of the biosensor, ensuring precise and reliable results in a short time. The proposed sensor was operated at a constant applied potential of 0.35 V. After optimizing the system, a linear calibration curve was obtained for the concentration range of 1.0-40 mM (R2 = 0.986). The FI system was successfully applied to determine the glucose content of a commercial sports drink.

Aza-BODIPY-based polymeric nanoparticles for photothermal cancer therapy in a chicken egg tumor model.

A new push-pull aza-BODIPY (AZB-CF3) derivative comprised of dimethylamino groups and trifluoromethyl moieties was successfully synthesized. This derivative exhibited broad absorption in the near-infrared region in the range from 798 to 832 nm. It also exhibited significant near-infrared (NIR) signals in low-polar solvents with emission peaks around 835-940 nm, while non-fluorescence in high-polar environments due to the twisted intramolecular charge transfer (TICT) phenomenon. The nanoprecipitation of this compound with phospholipid-based polyethylene glycol (DSPE-PEG) yielded AZB-CF3@DSPE-PEG nanoparticles (NPs) with a hydrodynamic size of 70 nm. The NPs exhibited good photostability, colloidal stability, biocompatibility, and excellent photothermal (PTT) competence with a conversion efficiency (η) of 44.9%. These NPs were evaluated in vitro and in ovo in a 4T1 breast cancer cell line for NIR light-trigger photothermal therapy. Proven in the chicken egg tumor model, AZB-CF3@DSPE-PEG NPs induced severe vascular damage (∼40% vascular destruction), showed great anticancer efficacy (∼75% tumor growth inhibition), and effectively inhibited distant metastasis via photothermal treatment. As such, this PTT-based nanocarrier system could be a potential candidate for a clinical cancer therapy approach.

Revolutionary Pyrazole-based Aza-BODIPY: Harnessing Photothermal Power Against Cancer Cells and Bacteria.

In the realm of cancer therapy and treatment of bacterial infection, photothermal therapy (PTT) stands out as a potential strategy. The challenge, however, is to create photothermal agents that can perform both imaging and PTT, a so-called theranostic agent. Photothermal agents that absorb and emit in the near-infrared region (750-900 nm) have recently received a lot of attention due to the extensive penetration of NIR light in biological tissues. In this study, we combined pyrazole with aza-BODIPY (PY-AZB) to develop a novel photothermal agent. PY-AZB demonstrated great photostability with a photothermal conversion efficiency (PCE) of up to 33 %. Additionally, PY-AZB can permeate cancer cells at a fast accumulation rate in less than 6 hours, according to the confocal images. Furthermore, in vitro photothermal therapy results showed that PY-AZB effectively eliminated cancer cells by up to 70 %. Interestingly, PY-AZB exhibited antibacterial activities against both gram-negative bacteria, Escherichia coli 780, and gram-positive bacteria, Staphylococcus aureus 1466. The results exhibit a satisfactory bactericidal effect against bacteria, with a killing efficiency of up to 100 % upon laser irradiation. As a result, PY-AZB may provide a viable option for photothermal treatment.

Heavy Atom Effect on the Intersystem Crossing of a Boron Difluoride Formazanate Complex-Based Photosensitizer: Experimental and Theoretical Studies.

Photodynamic therapy (PDT) is a photochemical-based treatment approach that involves using light to activate photosensitizers (PSs). Attractively, PDT is one of the alternative cancer treatments due to its noninvasive technique. By utilizing the heavy atom effect, this work modified a class of formazan dyes to improve intersystem crossing (ISC) to improve reactive oxygen species (ROS) generation for PDT treatment. Two methods were used to observe the ROS generation enhanced by ISC of the synthesized complexes including, (1) recording DPBF decomposition caused by the ROS, and (2) calculating the potential energy curves for photophysical mechanisms of BF2 -formazanate dyes using the DFT and nudged elastic band (NEB) methods. The photophysical properties of the dyes were studied using spectroscopic techniques and X-ray crystallography, as well as DFT calculations. The experimental and theoretical results and in vitro cellular assays confirmed the potential use of the newly synthesized iodinated BF2 -formazanate dyes in PDT.

Unraveling the photophysical characteristics and biological applications of vinyl sulfones as viscosity sensors.

For the first time, a series of vinyl sulfone-NH2-based push-pull fluorophores (4a-4d) were introduced for their potential use in biological applications. The fluorophores 4a-4d were readily synthesized upon reduction of the corresponding vinyl sulfones-NO2 (3a-3d), which were prepared by sulfonylation of nitrostyrene. Both types of probes can be prepared in high yields through a few steps with minimal cost. In diverse solvents, probes 4a-4d exhibited fluorescence with strong emission peaking around 403-490 nm. Additionally, the fluorescence intensity of probe 4d rose approximately 85-fold with increasing viscosity. The probes 4a-4d demonstrated good stability and photostability in a broad pH range. Moreover, probes 4a-4d showed significantly improved biocompatibility compared to those derived from 3a-3d. For cell imaging applications, the developed probes 4a-4d exhibited much stronger blue fluorescence in cancer cells (HepG2) compared to 3a-3d. In addition, probes 4a-4d exhibited low cytotoxicity within 24 h toward both cancer and normal cells (HEK-293). Interestingly, probe 4d showed great sensitivity to viscosity in cancer cells. As a result, readily prepared vinyl sulfone-NH2-based push-pull fluorophores (4a-4d) offer a promising strategy for further development as cancer cell staining agents.

Quinoline-Malononitrile-Based Aggregation-Induced Emission Probe for Monoamine Oxidase Detection in Living Cells.

A quinoline-malononitrile (QM)-based aggregation-induced emission probe was developed to detect MAOs in cells through an enzymatic reaction followed by ß-elimination. After being incubated at 37 °C, QM-NH2 responded to the MAO enzymes with great specificity and within just 5 min. This 5 min responsive mechanism was fast, with the limit of detection (LOD) at 5.49 and 4.76 µg mL-1 for MAO-A and MAO-B, respectively. Moreover, QM-NH2 displayed high enzyme specificity even in the presence of high concentrations of biological interferences, such as oxidizing and reducing agents, biothiols, amino acids, and glucose. Furthermore, QM-NH2 demonstrated biocompatibility as the cells retained more than 70% viability when exposed to QM-NH2 at concentrations of up to 20 µM. As a result, QM-NH2 was used to detect MAO-A and MAO-B in SH-SY5Y and HepG2 cells, respectively. After 1h incubation with QM-NH2, the cells exhibited enhanced fluorescence by about 20-fold. Moreover, the signal from cells was reduced when MAO inhibitors were applied prior to incubating with QM-NH2. Therefore, our research recommends using a QM probe as a generic method for producing recognition moieties for fluorogenic enzyme probes.

Quercetin Nanoparticle-Based Hypoxia-Responsive Probe for Cancer Detection.

In this study, we developed functional nanomaterials via a phenolic-enabled nanotechnology strategy for hypoxia detection employing quercetin (QCT), an abundant flavonoid, as a polyphenolic system. The nano form of QCT was stabilized by coating it with polyethylene glycol (PEG) before loading it with a flavylium dye (Flav) as a pH indicator. The nanosystem, Flav@QCT-PEG, collapsed when it was in an acidic environment, i.e., pH 5, leading to the release of Flav, which activated the fluorescent signal. Therefore, Flav@QCT-PEG was applied to detect hypoxic tumors, known to be acidic, and responded to hypoxic environments in a dose- and time-dependent manner.

Hybrid Cyanine/Methotrexate Nanoparticles for Synergistic PDT/Chemotherapy of Breast Cancer.

Typically, nanomedicine was prepared using a nanocarrier to load cargo for specific purposes. In this work, a carrier-free nanosystem for imaging and photodynamic (PDT)/chemo combination therapy was developed using simple self-assembly of a dye and a chemotherapeutic agent. The resulting nanoparticles (I2-IR783/MTX@NPs) exhibited a spherical morphology with a size of 240.6 ± 2.5 nm. I2-IR783/MTX@NPs had substantial internalization in 4T1 murine breast cancer cells and showed a synergistic anticancer effect after NIR light irradiation. Additionally, the 3D tumor model exhibits the same phototoxicity of nanoparticles as a 2D cell culture. The PDT efficiency of the nanosystem in the physiological environment was confirmed by the detection of intracellular reactive oxygen species as well as the live/dead viability/cytotoxicity assay following NIR light exposure. In addition, optical coherence tomography (OCT) was used as an alternative tool to monitor the response after treatment. Therefore, I2-IR783/MTX@NPs show great potential use in theranostic application for breast cancer PDT-chemotherapy.

BODIPY-Based Fluorescent Probes for Selective Visualization of Endogenous Hypochlorous Acid in Living Cells via Triazolopyridine Formation.

In this work, the two pyridylhydrazone-tethered BODIPY compounds (2 and 3) were synthesized. These compounds aimed to detect hypochlorous acid (HOCl) species via cyclic triazolopyridine formation. The open forms and the resulting cyclic forms of BODIPYs (2, 3, 4, and 5) were fully characterized by nuclear magnetic resonance, mass spectrometry, infrared spectroscopy, and single-crystal X-ray diffraction. These two probes can selectively detect HOCl through a fluorescence turn-on mechanism with the limit of detections of 0.21 µM and 0.77 µM for compounds 2 and 3, respectively. This fluorescence enhancement phenomenon could be the effect from C = N isomerization inhibition due to HOCl-triggered triazolopyridine formation. In cell imaging experiments, these compounds showed excellent biocompatibility toward RAW 264.7 murine live macrophage cells and greatly visualized endogenous HOCl in living cells stimulated with lipopolysaccharide.

Aza-BODIPY based carbonic anhydrase IX: Strategy to overcome hypoxia limitation in photodynamic therapy.

Hypoxia caused by photodynamic therapy (PDT) is a major hurdle to cancer treatment since it can promote recurrence and progression by activating angiogenic factors, lowering therapeutic efficacy dramatically. In this work, AZB-I-CAIX2 was developed as a carbonic anhydrase IX (CAIX)-targeting NIR photosensitizer that can overcome the challenge by utilizing a combination of CAIX knockdown and PDT. AZB-I-CAIX2 showed a specific affinity to CAIX-expressed cancer cells and enhanced photocytotoxicity compared to AZB-I-control (the molecule without acetazolamide). Moreover, selective detection and effective cell cytotoxicity of AZB-I-CAIX2 by PDT in hypoxic CAIX-expressed murine cancer cells were achieved. Essentially, AZB-I-CAIX2 could minimize tumor size in the tumor-bearing mice compared to that in the control groups. The results suggested that AZB-I-CAIX2 can improve therapeutic efficiency by preventing PDT-induced hypoxia through CAIX inhibition.

A facile method for generating polypyrrole microcapsules and their application in electrochemical sensing.

A facile and rapid strategy to generate polypyrrole microcapsules is reported. The strategy is compatible with a vortex mixer and with a microfluidic chip for droplet generation, allowing a > 100-fold reduction in particle size. The sub-micron particle sizes obtained can also be tuned to some extent based on the chip geometry. The capsules can be kept stably in solution and can be transferred onto electrochemical devices. As an application example, we casted the polypyrrole capsules generated onto screen-printed electrodes, leading to a significant increase in their electroactive surface area and capacitance. The electrodes were further modified with glucose dehydrogenase (GDH) to fabricate glucose biosensors. The introduction of polypyrrole microcapsules increased the dynamic range of the glucose sensor to ca. 300% compared with that of the electrode without polypyrrole microcapsules. The resulting glucose sensor is operated at a constant applied potential of 0.20 V vs. Ag/AgCl (3 M KCl) in an air-equilibrated electrolyte. At this potential, the sensor showed a linear range from 1.0 to 9.0 mM glucose with a sensitivity of 3.23 µA cm-2 mM-1 (R2 = 0.993). The limit of detection obtained was 0.09 mM, and the reproducibility was 3.6%. The method allows generating polypyrrole microcapsules without surfactants or organic solvents and may enable new opportunities in the design of biosensors, electronic devices, and molecular delivery.

Hemicyanine-based pH-responsive probes for rapid hypoxia detection in cancer cells.

As pH-sensitive and hypoxia-responsive probes, three hemicyanine derivatives based on vanillin and the indole ring (Val-Hcys) were synthesized. The fluorescence of the probes can be activated at acidic pH using the amide functionalized sidechains. Furthermore, when Val-Hcys were incubated with hypoxic cells for 5 min, the fluorescent signals significantly increased when compared to normoxia cells (4-fold enhancement, maximum at 180 min). In addition, Val-Hcys tend to accumulate in lysosomes and mitochondria, two important organelles involved in cell mitophagy. Surprisingly, Val-Hcys improved cell viability in hypoxic conditions. As a result, this study demonstrates the utility of Val-Hcys as pH-responsive probes for detecting hypoxic areas.

PEGylated Aza-BODIPY Nanoparticles for Photothermal Therapy.

Photothermal therapy is a promising treatment modality in the realm of cancer therapy. Photothermal nanomaterials that absorb and emit in the near-infrared range (750-900 nm) have drawn a lot of attention recently because of the deep penetration of NIR light in biological tissue. Most nanomaterials, however, are produced by encapsulating or altering the surface of a nanoplatform, which has limited loading capacity and long-term storage. Herein, we developed a stable polymer conjugated with aza-BODIPY that self-assembled to form nanoparticles (aza-BODIPY-mPEG) with better hydrophilicity and biocompatibility while retaining the dye's photothermal conversion characteristics. Aza-BODIPY-mPEG with a hydrodynamic size of around 170 nm exhibited great photostability and excellent photothermal therapy in vitro and in ovo. Aza-BODIPY-mPEG exhibits approximately 30% better anti-angiogenesis and antitumor activity against implanted xenograft human HCT116 tumor in the chick embryo compared to parent aza-BODIPY-A, altogether suggesting that aza-BODIPY-mPEG is a promising material for cancer photothermal therapy.

Electrodeposition of Cobalt Oxides on Carbon Nanotubes for Sensitive Bromhexine Sensing.

We develop an electrochemical sensor for the determination of bromhexine hydrochloride (BHC), a widely use mucolytic drug. The sensor is prepared by electrodeposition of cobalt oxides (CoOx) on a glassy carbon electrode modified with carboxylated single-walled carbon nanotubes (SWCNT). A synergistic effect between CoOx and SWCNT is observed, leading to a significant improvement in the BHC electrooxidation current. Based on cyclic voltammetry studies at varying scan rates, we conclude that the electrochemical oxidation of BHC is under mixed diffusion-adsorption control. The proposed sensor allows the amperometric determination of BHC in a linear range of 10-500 µM with a low applied voltage of 0.75 V. The designed sensor provides reproducible measurements, is not affected by common interfering substances, and shows excellent performance for the analysis of BHC in pharmaceutical preparations.

Indomethacin-based near-infrared photosensitizer for targeted photodynamic cancer therapy.

Near-IR fluorescent sensitizers based on heptamethine cyanine (Cy820 and Cy820-IMC) were synthesized and their abilities to target and abolish tumor cells via photodynamic therapy (PDT) were explored. Some hepthamethine cyanine dyes can be transported into cancer cells via the organic anion transporting polypeptides (OATPs). In this study, we aimed to enhance the target ability of the sensitizer by conjugation Cy820 with indomethacin, a non-steroidal anti-inflammatory drug (NSAID), to obtain Cy820-IMC that aimed to target cyclooxygenase-2 (COX-2) which overexpresses in cancer cells. The results showed that Cy820-IMC internalized the cancer cells faster than Cy820 which was verified to be related to COX-2 level and OATPs. Based on PDT experiments, Cy820-IMC has higher photocytotoxicity index than Cy820, >7.13 and 4.90, respectively, implying that Cy820-IMC showed better PDT property than Cy820. However, Cy820 exhibits slightly higher normal-to-cancer cell toxicity ratio than Cy820-IMC, 6.58 and 3.63, respectively. Overall, Cy820-IMC has superior cancer targetability and enhanced photocytoxicity. These characteristics can be further improved towards clinically approved sensitizers for PDT.