Search Results (371)

Phthalocyanines (Pcs) are well-established photosensitizers in photodynamic therapy, valued for their strong light absorption, high singlet oxygen generation, and photostability. Recent advances have focused on covalently conjugating Pcs, particularly zinc phthalocyanines (ZnPcs), with a wide range of small bioactive molecules to improve selectivity, efficacy, and multifunctionality. These conjugates combine light-activated reactive oxygen species (ROS) production with targeted delivery and controlled release, offering enhanced treatment precision and reduced off-target toxicity. Chemotherapeutic agent conjugates, including those with erlotinib, doxorubicin, tamoxifen, and camptothecin, demonstrate receptor-mediated uptake, pH-responsive release, and synergistic anticancer effects, even overcoming multidrug resistance. Beyond oncology, ZnPc conjugates with antibiotics, anti-inflammatory drugs, antiparasitics, and antidepressants extend photodynamic therapy’s scope to antimicrobial and site-specific therapies. Targeting moieties such as folic acid, biotin, arginylglycylaspartic acid (RGD) and epidermal growth factor (EGF) peptides, carbohydrates, and amino acids have been employed to exploit overexpressed receptors in tumors, enhancing cellular uptake and tumor accumulation. Fluorescent dye and porphyrinoid conjugates further enrich these systems by enabling imaging-guided therapy, efficient energy transfer, and dual-mode activation through pH or enzyme-sensitive linkers. Despite these promising strategies, key challenges remain, including aggregation-induced quenching, poor aqueous solubility, synthetic complexity, and interference with ROS generation. In this review, the examples of Pc-based conjugates were described with particular interest on the synthetic procedures and optical properties of targeted compounds. Full article

Background: Pain is a complex phenomenon characterized by unpleasant experiences with profound heterogeneity influenced by biological, psychological, and social factors. According to the National Health Interview Survey, 50.2 million U.S. adults (20.5%) experience pain on most days, with the annual cost of prescription medication for pain reaching approximately USD 17.8 billion. Theranostic pain nanomedicine therefore emerges as an attractive analgesic strategy with the potential for increased efficacy, reduced side-effects, and treatment personalization. Theranostic nanomedicine combines drug delivery and diagnostic features, allowing for real-time monitoring of analgesic efficacy in vivo using molecular imaging. However, clinical translation of these nanomedicines are challenging due to complex manufacturing methodologies, lack of standardized quality control, and potentially high costs. Quality by Design (QbD) can navigate these challenges and lead to the development of an optimal pain nanomedicine. Our lab previously reported a macrophage-targeted perfluorocarbon nanoemulsion (PFC NE) that demonstrated analgesic efficacy across multiple rodent pain models in both sexes. Here, we report PFC-free, biphasic nanoemulsions formulated with a biocompatible and non-immunogenic plant-based coconut oil loaded with a COX-2 inhibitor and a clinical-grade, indocyanine green (ICG) near-infrared fluorescent (NIRF) dye for parenteral theranostic analgesic nanomedicine. Methods: Critical process parameters and material attributes were identified through the FMECA (Failure, Modes, Effects, and Criticality Analysis) method and optimized using a 3 × 2 full-factorial design of experiments. We investigated the impact of the oil-to-surfactant ratio (w/w) with three different surfactant systems on the colloidal properties of NE. Small-scale (100 mL) batches were manufactured using sonication and microfluidization, and the final formulation was scaled up to 500 mL with microfluidization. The colloidal stability of NE was assessed using dynamic light scattering (DLS) and drug quantification was conducted through reverse-phase HPLC. An in vitro drug release study was conducted using the dialysis bag method, accompanied by HPLC quantification. The formulation was further evaluated for cell viability, cellular uptake, and COX-2 inhibition in the RAW 264.7 macrophage cell line. Results: Nanoemulsion droplet size increased with a higher oil-to-surfactant ratio (w/w) but was no significant impact by the type of surfactant system used. Thermal cycling and serum stability studies confirmed NE colloidal stability upon exposure to high and low temperatures and biological fluids. We also demonstrated the necessity of a solubilizer for long-term fluorescence stability of ICG. The nanoemulsion showed no cellular toxicity and effectively inhibited PGE2 in activated macrophages. Conclusions: To our knowledge, this is the first instance of a celecoxib-loaded theranostic platform developed using a plant-derived hydrocarbon oil, applying the QbD approach that demonstrated COX-2 inhibition. Full article

This study presents research on the production of activated biocarbons derived from herbal waste. Sage stems were chemically activated with two activating agents of different chemical natures—H₃PO₄ and K₂CO₃—and subjected to two thermal treatment methods: conventional and microwave heating. The effect of the activating agent type and heating method on the basic physicochemical properties of the resulting activated biocarbons was investigated. These properties included surface morphology, elemental composition, ash content, pH of aqueous extracts, the content and nature of surface functional groups, points of zero charge, and isoelectric points, as well as the type of porous structure formed. In addition, the potential of the prepared carbonaceous materials as adsorbents of model organic (represented by Triton X-100 and methylene blue) and inorganic (represented by iodine) pollutants was assessed. The influence of the initial adsorbate concentration (5–150 (dye) and 10–800 mg/dm³ (surfactant)), temperature (20–40 °C), and pH (2–10) of the system on the efficiency of contaminant removal from aqueous solutions was evaluated. The adsorption kinetics were also investigated to better understand the rate and mechanism of contaminant uptake by the prepared activated biocarbons. The results showed that materials activated with orthophosphoric acid exhibited a significantly higher sorption capacity for all tested adsorbates compared to their potassium carbonate-activated counterparts. Microwave heating was found to be more effective in promoting the formation of a well-developed specific surface area (471–1151 m²/g) and porous structure (mean pore size 2.17–3.84 nm), which directly enhanced the sorption capacity of both organic and inorganic contaminants. The maximum adsorption capacities for iodine, methylene blue, and Triton X-100 reached the levels of 927.0, 298.4, and 644.3 mg/g, respectively, on the surface of the H₃PO₄-activated sample obtained by microwave heating. It was confirmed that the heating method used during the activation step plays a key role in determining the physicochemical properties and sorption efficiency of activated biocarbons. Full article

Among the craft recipes for artisans collected in the 4th-century Egyptian documents the Leyden and Stockholm papyri, there is one calling for adding animal milk to orchil for wool dyeing. To understand the rationale for this practice, wool yarns were dyed with and without goat milk added to orchil dyebaths, each made using lichens from three different sources. The results showed orchil containing milk dyed yarns a noticeably deeper red hue. The colorants extracted from the dyed yarns were analyzed by liquid chromatography-diode-array-detector-mass spectrometry to assess the relative amounts of nine identifiable orceins. The data showed that the yarns dyed with milk gave extracts exhibiting several fold more α-aminoorcein and α-hydroxyorcein, with only small differences in the other seven. Scanning electron microscopic analysis of a representative pair of dyed yarns showed that milk promoted surface changes in the fiber that may indicate increased cutaneous damage. Hypotheses for the milk’s effects on orchil dyeing were proposed that included the formation of milk–protein complexes with the two enriched orceins that possibly enhanced wool binding and/or better wool uptake of free and/or complexed orceins due to biodegradation of the wool’s surface cuticle caused by microbial growth promoted by the addition of milk. Full article

Recent advancements in phototherapy have underscored the need for effective cellular imaging agents that can enhance therapeutic efficacy and precision. Perylene diimide (PDI) dyes, known for their unique optical properties and biocompatibility, have emerged as promising candidates in this domain. This review paper provides a comprehensive analysis of the potential applications of PDI dyes in cellular imaging, specifically within the context of phototherapies. We explore the synthesis of these dyes, their photophysical characteristics, and mechanisms of cellular uptake. Moreover, this review highlights recent studies that demonstrate the effectiveness of PDI dyes in the real-time imaging of cellular processes and their synergistic effects in photodynamic therapy (PDT) and photothermal therapy (PTT). By evaluating various experimental approaches and their outcomes, we aim to elucidate the advantages of employing PDI dyes in clinical settings. The findings of this review suggest that perylene diimide dyes are not only capable of enhancing imaging contrast but also optimizing the therapeutic response in targeted phototherapy applications. Ultimately, this paper advocates for further research into the integration of PDI dyes in clinical practice, emphasizing their potential to significantly improve patient outcomes in cancer and other diseases requiring photoactive treatment modalities. Full article

We have previously reported on a novel monoclonal antibody (mAb) we designated F5, which was raised against a glycopeptide derived from the tandem repeat (TR) region of Mucin-4 (MUC4), a heavily O-glycosylated protein that is overexpressed in many pancreatic cancer cells. This mAb was highly specific for the MUC4 glycopeptide antigen in glycan microarrays, ELISA and SPR assays, selectively stained tissue derived from advanced-stage tumors, and bound MUC4⁺ tumor cells in flow cytometry assays. The mAb was also unique in that it did not cross-react with other commercial anti-MUC4 mAbs that were raised in a similar but non-glycosylated TR sequence. Here we describe the selective conjugation of a novel near-infrared dye to this mAb and in vivo biodistribution of this labeled mAb to various MUC4-expressing tumors in mice. The labeled mAb were selectively distributed to both cell-derived xenograft (CDX) flank tumors and patient-derived xenograft (PDX) tumors that expressed MUC4 compared to those that were MUC4-negative. Organ distribution analysis showed high uptake in MUC4⁺ relative to MUC4⁻ tumors. These results suggest that mAb F5 may be used to develop MUC4-targeted, passive antibody-based immunotherapies against Pancreatic Ductal Adenocarcinomas (PDACs) which are notorious for being refractory to many chemo- and radiotherapies Full article

Mitochondrial transplantation (MTx) has emerged as a potential therapeutic approach for diseases associated with mitochondrial dysfunction, yet its scalability and cross-species feasibility remain underexplored. This study aimed to evaluate the dose-dependent uptake and molecular effects of xenogeneic mitochondrial transplantation (xeno-MTx) using rat-derived mitochondria in mouse neuronal systems. HT-22 hippocampal neuronal cells and a murine model of cardiac arrest-induced global cerebral ischemia were used to assess mitochondrial uptake, gene expression, and mitochondrial DNA presence. Donor mitochondria were isolated from rat pectoralis muscle and labeled with MitoTracker dyes. Flow cytometry and confocal microscopy revealed a dose-dependent increase in donor mitochondrial uptake in vitro. Quantitative PCR demonstrated a corresponding increase in rat-specific mitochondrial DNA and upregulation of Mfn2 and Bak1, with no changes in other fusion, fission, or apoptotic genes. Inhibitor studies indicated that mitochondrial internalization may involve actin-dependent macropinocytosis and cholesterol-sensitive endocytic pathways. In vivo, rat mitochondrial DNA was detected in mouse brains post–xeno-MTx, confirming donor mitochondrial delivery to ischemic tissue. These findings support the feasibility of xeno-MTx and its dose-responsive biological effects in neuronal systems while underscoring the need for further research to determine long-term functional outcomes and clinical applicability. Full article

Background/objectives: Hypoxia in the tumor microenvironment is linked to aggressiveness, epithelial–mesenchymal transition, metastasis, and therapy resistance. Targeting hypoxia to enhance antitumor immunity is crucial for overcoming therapeutic resistance. Here, we investigated the ability of Evofosfamide, a prodrug that gets activated under hypoxic conditions, to sensitize breast cancer cells to cell death. Evofosfamide is converted into bromo-isophosphoramide mustard, a potent DNA cross-linking agent that is expected to enhance the killing of cancer cells under hypoxic conditions, where these cells typically exhibit resistance. Methods: Representative breast cancer cell lines, MCF-7 and MDA-MB-231, were treated with Evofosfamide under normoxia and hypoxia. Changes in cell viability and the mechanism of cell death were measured using neutral red dye uptake, Annexin-FITC/propidium iodide staining, and Western blot analysis of markers—PARP1 and caspase 3/7. We tested Evofosfamide’s ability to counteract hypoxic suppression of type I Interferon signaling genes using quantitative PCR (qPCR), as well as its capacity to trigger natural killer (NK)-cell-mediated cytotoxicity. Results: Evofosfamide enhanced cell killing in both MCF-7 and MDA-MB-231 cells under hypoxic conditions compared to normoxic conditions. Cell killing was accompanied by increased cellular reactive oxygen species (ROS), diminished mitochondrial membrane potential, and induction of apoptosis, as demonstrated by the fragmentation or laddering of genomic DNA, the activation of caspase 3/7, and the cleavage of PARP. qPCR analysis revealed that Evofosfamide was capable of restoring type I interferon signaling in hypoxic breast cancer cells, leading to the subsequent cytolytic activity of NK cells against the tumor cells. Conclusions: Thus, conditioning the breast cancer cells with Evofosfamide resulted in enhanced cell killing under hypoxia, further underscoring its potential as a sensitizer to target hypoxia-driven tumors. Full article

Bio-based polyamide 56 (PA56) is a new sustainable material in the polyamide family. In this study, dyes suitable for PA56 fibers were experimentally screened from natural plants rich in pigments. The results showed that the preferred natural dyes for PA56 fabric are turmeric for a yellow hue, madder for a red hue, catechu for a brown hue, and indigo for a blue hue. A green hue was achieved by the two-bath dyeing method using indigo and turmeric, respectively. For a dyability comparison with conventional PA6 and PA66, PA56, PA6, and PA66 fabrics were woven under identical conditions and dyed with turmeric, madder, catechu, and commercial indigo extracts. PA56 fabric exhibited the best dye uptake and the fastest dyeing rate (PA56 > PA6 > PA66). The reason for the excellent dyeability of PA56 fibers was analyzed in terms of differential scanning calorimetry measurement and molecular dynamics simulations. The results showed that the lowest crystallinity was exhibited by PA56 (PA56 < PA6 < PA66); in addition, PA56 displayed the largest fractional free volume (PA56 > PA6 > PA66). These structural characteristics contribute to the excellent dyeability of PA56 fibers. Therefore, PA56 fibers are promising materials, as they are derived from a sustainable source and have superior dyeing properties compared to PA6 and PA66 fibers. Full article

This research investigates the adsorption potential of four types of adsorbents produced from agro-industrial waste (grape pomace—GP, tree pruning—TP, sugarcane bagasse—SB, and eucalyptus sawdust—ES) for the uptake of thiazine dye methylene blue (MB) from aqueous solution. A kinetic model based on a hybrid-order rate equation was fitted to experimental data. The result showed that BGP-300 presented the highest mass yield (58.84%) and energy yield (69.56%), followed by BTP-300 > BES-300 > BSB-300. Adsorption studies showed that BGP-300 had a better performance in the uptake of MB, with a removal efficiency (R_e) of 96.5% and adsorption capacity at equilibrium (q_e) of 9.3 mg g⁻¹, followed by tree pruning biochar (BTP-300), with an R_e of 65.0% and q_e of 5.3 mg g⁻¹. Meanwhile, eucalyptus sawdust (BES-300) and sugarcane bagasse (BSB-300) biochar did not facilitate any significant removal of MB. Adsorption kinetics is best described by a second-order rate with R² varying from 0.75 to 0.96. Desorption studies show a low concentration released to the solution, indicating that adsorption may occur physically and chemically. Therefore, this research provides comprehensive insights into the adsorption characteristics of different biochars, emphasizing the potential of torrefied materials BGP-300 and BTP-300 as effective for MB uptake from aqueous solution. Full article

Near-infrared photoimmunotherapy (NIR-PIT) is a promising cancer treatment that uses near-infrared light to activate a conjugate of a monoclonal antibody (mAb) and a photoactivatable silica phthalocyanine dye (IRDye700DX: IR700). Unlike conventional photodynamic therapy (PDT), NIR-PIT selectively destroys targeted tumor cells while preserving the surrounding normal tissue and providing superior tissue penetration. Recently, NIR-PIT has been approved for the treatment of unresectable recurrent head and neck cancers in Japan. It induces highly selective cancer cell death; therefore, it is expected to be a new curative treatment option for various cancers, including brain tumors. In this review, we compare the principles of NIR-PIT and PDT and discuss the potential applications of NIR-PIT for brain tumors. We selected targetable proteins across various types of brain tumors and devised a strategy to effectively pass the mAb–IR700 conjugate through the blood–brain barrier (BBB), which is a significant challenge for NIR-PIT in treating brain tumors. Innovative approaches for delivering the mAb–IR700 conjugate across the BBB include exosomes, nanoparticle-based systems, and cell-penetrating peptides. Small-molecule compounds, such as affibodies, are anticipated to rapidly accumulate in tumors within intracranial models, and our preliminary experiments demonstrated rapid uptake. NIR-PIT also induces immunogenic cell death and activates the anti-tumor immune response. Overall, NIR-PIT is a promising approach for treating brain tumors. It has the potential to overcome the limitations of conventional therapies and offers new hope to patients with brain tumors. Full article

The widespread discharge of synthetic dyes such as Eriochrome Black T (EBT) into water bodies poses significant environmental and health concerns due to their toxicity, persistence, and resistance to degradation. In response to this issue, the removal of EBT dye from aqueous solutions using nickel-modified orange peel biochar (MOPB) was investigated in this study at various experimental conditions such as adsorbent dose, pH, concentration of dye, temperature, and contact time. Biochar was prepared from orange peels via pyrolysis, and structural characterization was performed using FTIR, XRD, and SEM to assess morphological changes, pore structure, and functional groups post-modification. MOPB exhibited significantly enhanced adsorption capacity compared to unmodified biochar. Optimal removal (at 0.1 g adsorbent dose, 25 ppm dye concentration, 90 min contact time, 35 °C, and pH 4) resulted in maximum EBT elimination. The equilibrium dataset was evaluated using Langmuir and Freundlich isotherm models. The Langmuir model (R² = 0.99) best described the uptake of EBT dye, which implies that the adsorption of EBT dye onto MOPB was monolayered. The kinetic data were also analyzed using pseudo-first-order and pseudo-second-order models. The pseudo-second-order kinetic model was found to be the best fit (R² = 0.99), indicating that it governs the rate-limiting step of the reaction. Thermodynamic parameters confirmed that the adsorption process is spontaneous and exothermic. These findings demonstrate the potential of MOPB as a low-cost, sustainable adsorbent for the efficient removal of EBT from industrial wastewater. Full article

The blood–brain barrier (BBB) limits drug delivery to the brain, particularly for large or hydrophilic molecules. Brain microvascular endothelial cells (bEND.3), which form part of the BBB, play a critical role in regulating drug uptake. This study investigates the use of cold atmospheric microplasma (CAM) to enhance membrane permeability and facilitate drug delivery in bEND.3 cells. CAM generates reactive oxygen species (ROS) that modulate membrane properties. We exposed bEND.3 cells to CAM at varying voltages (3, 3.5, 4, and 4.5 kV) and measured drug uptake using the fluorescent drug FD-150, fluorescence intensity, ROS levels, membrane lipid order, and membrane potential. The results showed a significant increase in fluorescence intensity and drug concentration in the plasma-treated cells compared to controls. ROS production, measured by DCFH-DA staining, was higher in the plasma-treated cells, supporting the hypothesis that CAM enhances membrane permeability through ROS-induced changes. Membrane lipid order, assessed using the LipiORDER probe, shifted from the liquid-ordered (Lo) to liquid-disordered (Ld) phase, indicating increased membrane fluidity. Membrane depolarization was detected with DisBAC2(3) dye, showing increased fluorescence in the plasma-treated cells. Cell viability, assessed by trypan blue and LIVE/DEAD™ assays, revealed transient damage at higher voltages (≥4 kV), with recovery after 24 h. These results suggest that CAM enhances drug delivery in bEND.3 cells by modulating membrane properties via ROS production and changes in membrane potential. CAM offers a promising strategy for improving drug delivery to the brain, with potential applications in brain-targeted therapies. Full article

Background: The global burden of obesity and type 2 diabetes mellitus is a significant contributor to mortality and disability in the modern world. In this regard, the modification of adipocyte metabolism has been identified as a promising approach to develop new genetic and cellular engineering therapeutics. In this study, we activate the expression of creatine kinase B (CKB), a key enzyme of a non-canonical futile cycle and the regulator of energy storage, to promote catabolic processes in mature adipocytes. Methods: The protein-coding sequence of CKB was amplified by PCR from Mus musculus brain mRNA. Lentiviral transduction was used to transfer the CKB sequence into mature adipocytes. Adipocyte metabolism was analyzed by radioisotope monitoring of labeled [3H]-2-deoxyglucose and [14C]-glucose. Confocal microscopy was applied to estimate lipid droplets morphology (BODIPY493/503 dye), mitochondrial membrane potential (JC-1 dye), and thermogenesis (ERthermAC dye). Results: After lentiviral delivery of the CKB-coding sequence, CKB mRNA level increased 75-fold and protein expression fivefold. CKB overexpression does not cause significant changes in lipid droplet morphology. Despite this, enhanced glucose uptake and reduced lipid synthesis under adrenergic stimulation are detected during CKB overexpression. CKB causes an increase in mitochondrial potential with no effect on thermogenesis in adipocytes. Conclusions: In this study, we have shown that CKB overexpression in mature adipocytes allows us to obtain adipocytes with high glucose uptake, potency of ATP synthesis, and suppressed lipogenesis. These genetically modified cells may potentially exhibit a favorable metabolic effect in the context of excessive nutrient utilization. Full article

Industrial hemp (Cannabis sativa L.) was investigated as a sustainable biosorbent for removing Congo Red (CR) and Remazol Brilliant Blue R (RBBR) from wastewater. The unmodified hemp biosorbent exhibited moderate but practically relevant sorption capacities (4.47 mg/g for CR; 2.44 mg/g for RBBR), outperforming several agricultural waste materials. Kinetic studies revealed rapid uptake, with CR following pseudo-first-order kinetics (t₁/₂ < 15 min) and RBBR fitting the Elovich model, indicating heterogeneous surface interactions. Equilibrium data showed CR adsorption was best described by the Temkin isotherm (R² = 0.983), while RBBR followed the Langmuir model (R² = 0.998), reflecting their distinct binding mechanisms. Thermodynamic analysis confirmed spontaneous (ΔG° < 0), exothermic (ΔH° ≈ −2 kJ/mol), and entropy-driven processes for both dyes. Molecular docking elucidated the structural basis for performance differences: CR’s stronger binding (−7.5 kcal/mol) involved weak noncovalent interaction arising from partial overlap between the π-electron cloud of an aromatic ring and σ-bonds C-C or C-H (π-σ stacking) and hydrogen bonds with cellulose, whereas RBBR’s weaker affinity (−5.4 kcal/mol) relied on weak intermolecular interaction between a hydrogen atom (from a C-H bond) and the π-electron system of an aromatic ring (C-H∙∙∙π interactions). This work establishes industrial hemp as an eco-friendly alternative for dye removal, combining renewable sourcing with multi-mechanism adsorption capabilities suitable for small-scale water treatment applications. Full article