Search Results (122)

Cervical cancer represents a significant global health challenge. Photodynamic therapy (PDT) appears to be a promising, minimally invasive alternative to standard treatments. However, the clinical efficacy of PDT is sometimes limited by the low solubility and aggregation of photosensitizers, their non-selective distribution in the body, hypoxia in the tumor microenvironment, and limited light penetration. Recent advances in nanoparticle and nanocomposite platforms have addressed these challenges by integrating multiple functional components into a single delivery system. By encapsulating or conjugating photosensitizers in biodegradable matrices, such as mesoporous silica, organometallic structures and core–shell construct nanocarriers increase stability in water and extend circulation time, enabling both passive and active targeting through ligand decoration. Up-conversion and dual-wavelength responsive cores facilitate deep light conversion in tissues, while simultaneous delivery of hypoxia-modulating agents alleviates oxygen deprivation to sustain reactive oxygen species generation. Controllable “motor-cargo” constructs and surface modifications improve intratumoral diffusion, while aggregation-induced emission dyes and plasmonic elements support real-time imaging and quantitative monitoring of therapeutic response. Together, these multifunctional nanosystems have demonstrated potent cytotoxicity in vitro and significant tumor suppression in vivo in mouse models of cervical cancer. Combining targeted delivery, controlled release, hypoxia mitigation, and image guidance, engineered nanoparticles provide a versatile and powerful platform to overcome the current limitations of PDT and pave the way toward more effective, patient-specific treatments for cervical malignancies. Our review of the literature summarizes studies on nanoparticles and nanocomposites used in PDT monotherapy for cervical cancer, published between 2023 and July 2025. Full article

Background/Objectives: PEGylated liposomes are widely recognized for their biocompatibility and capacity to extend systemic circulation via “stealth” properties. However, the PEG corona often limits tumor penetration and cellular internalization. Targeting matrix metalloproteinase-2 (MMP-2), frequently upregulated in breast cancer stroma, presents an opportunity to enhance tissue-specific drug delivery. In this study, we engineered MMP-2-responsive GPLGVRG peptide-modified cleavable PEGylated liposomes for targeted paclitaxel (PTX) delivery. Methods: Molecular docking simulations employed the MMP-2 crystal structure (PDB ID: 7XJO) to assess GPLGVRG peptide binding affinity. A cleavable, enzyme-sensitive peptide-PEG conjugate (Chol-PEG_2K-GPLGVRG-PEG_5K) was synthesized via small-molecule liquid-phase synthesis and characterized by ¹H NMR and MALDI-TOF MS. Liposomes incorporating this conjugate (S-Peps-PEG_5K) were formulated to evaluate whether MMP-2-mediated peptide degradation triggers detachment of long-chain PEG moieties, thereby enhancing internalization by 4T1 breast cancer cells. Additionally, the effects of tumor microenvironmental pH (~6.5) and MMP-2 concentration on drug release dynamics were investigated. Results: Molecular docking revealed robust GPLGVRG-MMP-2 interactions, yielding a binding energy of −7.1 kcal/mol. The peptide formed hydrogen bonds with MMP-2 residues Tyr A:23 and Arg A:53 (bond lengths: 2.4–2.5 Å) and engaged in hydrophobic contacts, confirming MMP-2 as the primary recognition site. Formulations containing 5 mol% Chol-PEG_2K-GPLGVRG-PEG_5K combined with 0.15 µg/mL MMP-2 (S-Peps-PEG_5K +MMP) exhibited superior internalization efficiency and significantly reduced clonogenic survival compared to controls. Notably, acidic pH (~6.5) induced MMP-2-mediated cleavage of the GPLGVRG peptide, accelerating S-Peps-PEG_5K dissociation and facilitating drug release. Conclusions: MMP-2-responsive, cleavable PEGylated liposomes markedly improve PTX accumulation and controlled release at tumor sites by dynamically modulating their stealth properties, offering a promising strategy to enhance chemotherapy efficacy in breast cancer. Full article

Antioxidant nanomaterials, particularly mesoporous silica nanoparticles (MSNs) functionalized with polyphenols, offer innovative solutions for protecting oxidation-sensitive components and enhancing bioavailability in pharmaceuticals or extending the shelf life of nutraceutical and food products. This study investigates the influence of MSNs functionalized with caffeic acid (MSN-CAF) on powder flow properties and their tableting performance. Aminated MSNs were synthesized via co-condensation and conjugated with caffeic acid using EDC/NHS chemistry. Antioxidant capacity was evaluated using DPPH^●, ABTS^●+, ORAC, and FRAP assays. Powder blends with varying MSN-CAF concentrations (10–70%) were characterized for flow properties (angle of repose, Hausner ratio, Carr’s index), tablets were produced via direct compression, and critical quality attributes (weight uniformity, hardness, friability, disintegration, nanoparticle release) were assessed. MSN-CAF exhibited reduced antioxidant capacity compared with free caffeic acid due to pore entrapment but retained significant activity. Formulation F1 (10% MSN-CAF) showed excellent flowability (angle of repose: 12°, Hausner ratio: 1.16, Carr’s index: 14%), enabling robust tablet production with rapid disintegration, low friability, and complete nanoparticle release in 10 min. Additionally, the antioxidant nanomaterial demonstrated biocompatibility with the HepG2 cell line. MSN-CAF is a versatile nanoexcipient for direct compression tablets, offering potential as an active packaging agent and delivery system in the nutraceutical and food industries. Full article

Escherichia coli and Klebsiella pneumoniae are major contributors to the global challenge of antimicrobial resistance, posing serious threats to public health. Among current preventive strategies, conjugate vaccines that utilize bacterial surface polysaccharides have emerged as a promising and effective approach to counter multidrug-resistant strains. In this study, both the Wzy/Wzx-dependent and ABC transporter-dependent biosynthetic pathways for antigenic polysaccharides were introduced into E. coli W3110 cells. This dual-pathway engineering enabled the simultaneous biosynthesis of two structurally distinct polysaccharides within a single host, offering a streamlined and potentially scalable strategy for vaccine development. Experimental findings confirmed that both polysaccharide types were successfully produced in the engineered strains, although co-expression levels were moderately reduced. A weak competitive interaction was noted during the initial phase of induction, which may be attributed to competition for membrane space or the shared use of activated monosaccharide precursors. Interestingly, despite a reduction in plasmid copy number and transcriptional activity of the biosynthetic gene clusters over time, the overall polysaccharide yield remained stable with prolonged induction. This suggests that extended induction does not adversely affect final product output. Additionally, two glycoproteins were efficiently generated through in vivo bioconjugation of the synthesized polysaccharides with carrier proteins, all within the same cellular environment. This one-cell production system simplifies the workflow and enhances the feasibility of generating complex glycoprotein vaccines. Whole-cell proteomic profiling followed by MFUZZ clustering and Gene Ontology analysis revealed that core biosynthetic genes were grouped into two functional clusters. These genes were predominantly localized to the cytoplasm and were enriched in pathways related to translation and protein binding. Such insights not only validate the engineered biosynthetic routes but also provide a molecular basis for optimizing future constructs. Collectively, this study presents a robust synthetic biology platform for the co-expression of multiple polysaccharides in a single bacterial host. The approach holds significant promise for the rational design and production of multivalent conjugate vaccines targeting drug-resistant pathogens. Full article

Free radicals and inflammation have pivotal role in various degenerative diseases like cancer, rheumatoid arthritis, diabetes, cardiovascular and neurodegenerative disorders. Pyrazoles possess a wide range of biological activities such as antifungal, antituberculosis, antimicrobial, antiviral, anti-inflammatory, anti-convulsant, anticancer etc. In this present study a series of dibenzalacetones and the corresponding pyrazole hybrids were designed through bioisosterism, synthesized and biologically evaluated to highlight the importance of the extended conjugated system and substitution to the anti-inflammatory and antioxidant activity. The synthesis of dibenzalacetones was achieved via Claisen-Schmidt reaction. The dihydro-pyrazoles were synthesized from the substituted dibenzacetones and phenylhydrazines, hydrazine and semicarbazide under microwave irradiation optimizing reaction conditions. The synthesized compounds were spectroscopically characterized and evaluated for their anti-lipid peroxidation (AAPH) activity, their interaction with the free radical DPPH and the inhibition of soybean LOX. The novel derivatives were studied in terms of their physicochemical properties. Many of the dihydro-pyrazoles showed potent antioxidant properties and significant inhibition of soybean lipoxygenase as a result of their physicochemical features. Compounds 4a and 4b presented the most potent anti-lipid peroxidation abilities (98% and 97%), whereas compounds 2d and 2e have proved to be the most potent lipoxygenase inhibitors with IC₅₀ values 2.5 μM and 0.35 μM. Moreover, docking studies with soybean lipoxygenase highlight the interactions of the novel derivatives with the enzyme. Full article

Understanding the catalytic behavior of heterogeneous systems for the copolymerization of ethylene with polar monomers is essential for developing advanced functional polyolefins. In this study, we conducted a quantum chemical investigation of the SiO₂-supported Ni–allyl–α-imine ketone catalyst (Ni-OH@SiO₂) to uncover the factors governing monomer insertion, selectivity, and reactivity. Using DFT calculations and energy decomposition analysis (ALMO-EDA), we evaluated the coordination and insertion of six industrially relevant polar monomers, comparing their behavior to ethylene homopolymerization. Our results show that special polar monomers (SPMs) with aliphatic spacers, such as vinyltrimethoxysilane (vTMS) and 5-hexenyl acetate (AMA), exhibit favorable insertion profiles due to enhanced electrostatic and orbital interactions with minimal steric hindrance. In contrast, fundamental polar monomers (FPMs), including methyl acrylate (MA) and vinyl chloride (vCl), show higher activation barriers and increased Pauli repulsion due to strong electron-withdrawing effects and conjugation with the vinyl group. AMA displayed the lowest activation barrier (7.4 kcal/mol) and highest insertion thermodynamic stability (−17.6 kcal/mol). These findings provide molecular-level insight into insertion mechanisms and comonomer selectivity in Ni–allyl catalysts supported on silica, extending experimental understanding. This work establishes key structure–reactivity relationships and offers design principles for developing efficient Ni-based heterogeneous catalysts for polar monomer copolymerization. Full article

A series of porphyrinoids fused to highly electron-withdrawing bis(thiadiazolo)benzene units have been prepared and spectroscopically characterized. These structures have modified chromophores and exhibit large bathochromic shifts. The nickel(II), copper(II) and zinc complexes of a bis(thiadiazolo)benzoporphyrin were prepared, and these showed strong absorptions above 600 nm that shifted to longer wavelengths with increasing atomic number for the coordinated metal cations. Although the investigated porphyrinoids were poorly soluble, proton NMR data could be obtained, and these demonstrated that the structures possess global aromatic character. This was confirmed with nucleus-independent chemical shift (NICS) calculations and anisotropy of induced current density (AICD) plots. The AICD plots also demonstrate that the fused heterocyclic unit is disconnected from the porphyrinoid π-system, and in this respect, it differs from phenanthroline-fused porphyrinoids as it shows the presence of extended conjugation pathways. Full article

This study seeks to develop and implement a non-enzymatic fluorescent labeling for immunoassay and immunochromatographic assay (ICAs) targeting SARS-CoV-2, to meet the extensive interest and need for effective COVID-19 diagnosis. In this manuscript, we delineate the development, synthesis, and evaluation of a novel quinone polymer zinc hybrid nanoarchitecture, referred to as polymerized alizarin red–inorganic hybrid nanoarchitecture (PARIHN), which integrates an antibody for direct use in fluorescent immunoassays, offering enhanced sensitivity, reduced costs, and improved environmental sustainability. The designed nanoarchitecture can enhance the sensitivity of the immunoassay and enable rapid results without the complexities associated with enzymes, such as their low stability and high cost. At first, a chitosan–alizarin polymer was synthesized utilizing quinone–chitosan conjugation chemistry (QCCC). Then, the chitosan–alizarin polymer was embedded with the detection antibody using zinc ion, forming PARIHN, which was proven to be a stable label with the ability to enhance the assay stability and sensitivity of the immunoassay. PARIHN can react with phenylboronic acid (PBA) or boric acid through its alizarin content to produce fluorescence signals with an LOD of 15.9 and 2.6 pm for PBA and boric acid, respectively, which is the first use of a boric acid derivative in signal generation in the immunoassay. Furthermore, PARIHN demonstrated high practicality in detecting SARS-CoV-2 nucleoprotein in fluorescence (PBA and boric acid) systems with an LOD of 0.76 and 10.85 pm, respectively. Furthermore, owing to the high brightness of our PARIHN fluorogenic reaction, our labeling approach was extended to immunochromatographic assays for SARS-CoV-2 with high sensitivity down to 9.45 pg/mL. Full article

Background: Fatty liver disease and obesity are among the most prevalent health conditions in modern society and have recently garnered significant attention. Semaglutide, a well-known anti-obesity drug, has been widely used for diabetes and obesity treatment; however, nanotherapeutics utilizing semaglutide have not yet been developed. Methods: A novel statin–lipid conjugate was synthesized using rosuvastatin and ursodeoxycholic acid, a liver-protective agent. This conjugate was then formulated with semaglutide through hydrophobic interactions to create a new nanoparticle system. The physicochemical properties of the nanoparticles were analyzed, and their therapeutic efficacy was evaluated in a high-fat diet (HFD)-induced animal model. Results: The statin–lipid conjugate was successfully synthesized, forming novel nanoparticles with semaglutide in an aqueous solution. These nanoparticles exhibited distinct properties compared to conventional semaglutide formulations. In animal experiments, the treatment group demonstrated a 30.24% reduction in body weight and a 46.80% improvement in liver function markers compared to the control group. Conclusions: This study introduces a novel semaglutide-based nanoparticle (SRLC NP) system that overcomes key limitations of conventional semaglutide therapy by providing enhanced bioavailability, extended circulation time, and improved cellular uptake. These findings highlight the potential of SRLC NPs as a clinically translatable nanotherapeutic approach for more effective, sustained, and patient-friendly obesity and fatty liver disease treatment. Full article

Lateral flow immunoassays (LFIAs) were integrated into microfluidic chips and tested to enhance point-of-care testing (POCT), with the aim of improving sensitivity and expanding the range of CRP detection. The microfluidic approach improves upon traditional methods by precisely controlling fluid speed, thus enhancing sensitivity and accuracy in CRP measurements. The microfluidic approach also enables a one-step detection system, eliminating the need for buffer solution steps and reducing the nitrocellulose (NC) pad area to just the detection test line. This approach minimizes the non-specific binding of conjugated antibodies to unwanted areas of the NC pad, eliminating the need to block those areas, which enhances the sensitivity of detection. The gold nanoparticle method detects CRP in the high-sensitivity range of 1–10 $\mu$g/mL, which is suitable for chronic disease monitoring. To broaden the CRP detection range, including infection levels beyond 10 $\mu$g/mL, fluorescent labels were introduced, extending the measuring range from 1 to 70 $\mu$g/mL. Experimental results demonstrate that integrating microfluidic technology significantly enhances operational efficiency by precisely controlling the flow rate and optimizing the mixing efficiency while reducing fabrication resources by eliminating the need for separate pads, making these methods suitable for resource-limited settings. Microfluidics also provides greater control over fluid dynamics compared to traditional LFIA methods, which contributes to enhanced detection sensitivity even with lower sample volumes and no buffer solution, helping to enhance the usability of POCT. These findings highlight the potential to develop accessible, accurate, and cost-effective diagnostic tools essential for timely medical interventions at the POC. Full article

Hydrogen sulfide (H₂S) is an important signaling molecule involved in various physiological and pathological processes, making its accurate detection in biological systems highly desirable. In this study, two fluorescent probes (M1 and M2) based on 1,8-naphthalimide were developed for H₂S detection via a nucleophilic aromatic substitution. M1 demonstrated high sensitivity and selectivity for H₂S in aqueous media, with a detection limit of 0.64 µM and a strong linear fluorescence response in the range of 0–22 µM of NaHS. The reaction kinetics revealed a rapid response, with a reaction rate constant of 7.56 × 10² M⁻¹ s⁻¹, and M1 was most effective in the pH range of 6–10. Mechanism studies using ¹H NMR titration confirmed the formation of 4-hydroxyphenyl-1,8-naphthalimide as the product of H₂S-triggered nucleophilic substitution. M1 was applied in MDA-MB-231 cells for cell imaging, in which M1 provided significant fluorescence enhancement upon NaHS treatment, confirming its applicability for detecting H₂S in biological environments. In comparison, M2, designed with extended conjugation for red-shifted emission, exhibited weaker sensitivity due to the reduced stability of its naphtholate product and lower solubility. These results demonstrate that M1 is a highly effective and selective fluorescent probe for detecting H₂S, providing a valuable resource for investigating the biological roles of H₂S in health and disease. Full article

Transformers are susceptible to the influences of complex power grid systems, which may induce three-phase unbalance in transformers, thereby threatening their safety and stable operation. To better understand multiphysics interactions within a transformer under a three-phase load unbalance, a coupled multiphysics model is established and validated for an oil-immersed transformer based on the finite element method. The electromagnetic characteristics, conjugate heat transfer, and thermal stress of the transformer under three-phase load unbalance are analyzed, and the impact on the transformer’s relative aging rate is further assessed. The results show that under three-phase load unbalance, winding losses are significantly influenced by the degree of unbalance, while core losses remain almost unaffected. The maximum difference in winding losses between phases can reach 9.6 times, with a total loss increase of approximately 17.31% at a 30% unbalance degree for Case 3. The mutual heating effect between adjacent windings intensifies with the degree of unbalance, leading to higher temperatures in low-loss windings and sustaining high thermal stress and expansion. Severe three-phase unbalance (e.g., 30% unbalance degree in Case 3) can be mitigated by reducing the transformer load rate to 90%, thereby reducing the relative aging rate to about 20% of that under full load and significantly extending the transformer’s insulation life. Full article

Tetrahydrofolate (THF), the biologically active form of folate, serves as a crucial carrier of one-carbon units essential for synthesizing cellular components such as amino acids and purine nucleotides in vivo. It also acts as an important precursor for the production of pharmaceuticals, including folinate and L-5-methyltetrahydrofolate (L-5-MTHF). In this study, we developed an efficient enzyme cascade system for the production tetrahydrofolate from folate, incorporating NADPH recycling, and explored its application in the synthesis of L-5-MTHF, a derivative of tetrahydrofolate. To achieve this, we first screened dihydrofolate reductases (DHFRs) from various organisms, identifying SmDHFR from Serratia marcescens as the enzyme with the highest catalytic activity. We then conducted a comparative analysis of formate dehydrogenases (FDHs) from different sources, successfully establishing an NADPH recycling system. To further enhance biocatalytic efficiency, we optimized key reaction parameters, including temperature, pH, enzyme ratio, and substrate concentration. To address the challenge of pH mismatch in dual-enzyme reactions, we employed an enzymatic microenvironment regulation strategy. This involved covalently conjugating SmDHFR with a superfolder green fluorescent protein mutant carrying 30 surface negative charges (−30sfGFP), using the SpyCatcher/SpyTag system. This modification resulted in a 2.16-fold increase in tetrahydrofolate production, achieving a final yield of 4223.4 µM. Finally, we extended the application of this tetrahydrofolate synthesis system to establish an enzyme cascade for L-5-MTHF production with NADH recycling. By incorporating methylenetetrahydrofolate reductase (MTHFR), we successfully produced 389.8 μM of L-5-MTHF from folate and formaldehyde. This work provides a novel and efficient pathway for the biosynthesis of L-5-MTHF and highlights the potential of enzyme cascade systems in the production of tetrahydrofolate-derived compounds. Full article

Background/Objectives: The incidence of Ceftazidime/Avibactam (CZA)-resistant Klebsiella pneumoniae isolate co-producing Klebsiella pneumoniae carbapenemase 2 (KPC-2) and Vietnamese extended-spectrum β-lactamase 25 (VEB-25) has been on the rise in Greece over the past five years. This study investigates the isolation of ST323 K. pneumoniae isolates co-resistant to CZA and cefiderocol (FDC) from colonized and infected patients in a single hospital in Athens. Methods: CZA-resistant K. pneumoniae strains were isolated from 5 ICU patients from 27 December 2023 to 22 January 2024. Antimicrobial susceptibility was tested against a panel of agents. Whole-genome sequencing of the isolates was carried out to identify the acquired resistance genes and mutations that were associated with CZA and FDC resistance. Results: The K. pneumoniae isolates belonged to ST323 and harbored bla_KPC-2 and bla_VEB-25. The isolates had a minimum inhibitory concentration (MIC) of >256 mg/L for CZA and 32 mg/L for FDC, due to the disrupted catecholate siderophore receptor Fiu. bla_VEB-25 was located on an IncC non-conjugative plasmid and on a ~14 kb multidrug resistance (MDR) region comprising 15 further acquired resistance genes. Transformation studies showed that the bla_VEB-25-carrying plasmid provided resistance to most of the β-lactams tested, including CZA. The isolates remained susceptible to carbapenems, imipenem/relebactam, and meropenem/vaborbactam. The plasmid harbored the citrate-dependent iron (III) uptake system (fecIRABCDE), which increased the MIC of FDC from ≤0.08 mg/L to 2 mg/L. Conclusions: The bla_VEB-25 gene was associated with IncC plasmids which are important contributors to the spread of key antibiotic resistance genes. Strict infection control measures must be elaborated upon to prevent the spread of extensively drug-resistant organisms such as those described here. Full article

Recently, nitrostilbenes characterized by two different or differently substituted aryl moieties, obtainable from the initial ring-opening of 3-nitrobenzo[b]thiophene with amines, have proved, by means of a stepwise double coupling with phenolic-type bidentate C/O nucleophiles, to be valuable precursors of oxygen-containing heteropolycycles and of fully conjugated systems therefrom via an efficient 6π-electrocyclization and final aromatization. Herein, the methodology is extended, after suitable optimization, to diverse heterophenols to afford new appealing heteropolycyclic systems of potential interest as drug leads. The synthetic results are fully consistent with up-to-date quantomechanical calculations. For some of the new molecules, a significant fluorescence is reported, with a potential for future applications, e.g., in the field of optical devices. Full article