Search Results (67)

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/Objectives: The rapid emergence of multidrug-resistant bacterial infections demands innovative non-antibiotic therapeutic strategies. Dual-modal photoresponse therapy integrating photodynamic (PDT) and photothermal (PTT) effects offers a promising rapid antibacterial approach, yet designing single-material systems with synergistic enhancement remains challenging. This study aims to develop uniform Cu-based metal–organic framework micrometer cubes (Cu-BN) for efficient PDT/PTT synergy. Methods: Cu-BN cubes were synthesized via a one-step hydrothermal method using Cu(NO₃)₂ and 2-amino-p-benzoic acid. The material’s dual-mode responsiveness to visible light (420 nm) and near-infrared light (808 nm) was characterized through UV–Vis spectroscopy, photothermal profiling, and reactive oxygen species (ROS) generation assays. Antibacterial efficacy against multidrug-resistant Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) was quantified via colony counting under dual-light irradiation. Results: Under synergistic 420 + 808 nm irradiation for 15 min, Cu-BN (200 μg/mL) achieved rapid eradication of multidrug-resistant E. coli (99.94%) and S. aureus (99.83%). The material reached 58.6 °C under dual-light exposure, significantly exceeding single-light performance. Photodynamic analysis confirmed a 78.7% singlet oxygen (¹O₂) conversion rate. This enhancement stems from PTT-induced membrane permeabilization accelerating ROS diffusion, while PDT-generated ROS sensitized bacteria to thermal damage. Conclusions: This integrated design enables spatiotemporal PDT/PTT synergy within a single Cu-BN system, establishing a new paradigm for rapid-acting, broad-spectrum non-antibiotic antimicrobials. The work provides critical insights for developing light-responsive biomaterials against drug-resistant infections. Full article

Inflammatory Bowel Disease (IBD), which includes ulcerative colitis (UC) and Crohn’s disease (CD), results from dysregulated immune responses that drive chronic intestinal inflammation. Neutrophils, as key effectors of the innate immune system, contribute to IBD through multiple mechanisms, including the release of reactive oxygen species (ROS), pro-inflammatory cytokines, and neutrophil extracellular traps (NETs). NETs are web-like structures composed of DNA, histones, and associated proteins including proteolytic enzymes and antimicrobial peptides. NET formation is increased in IBD and has a context-dependent role; under controlled conditions, NETs support antimicrobial defense and tissue repair, whereas excessive or dysregulated NETosis contributes to epithelial injury, barrier disruption, microbial imbalance, and thrombotic risk. This review examines the roles of neutrophils and NETs in IBD. We summarize recent single-cell and spatial-omics studies that reveal extensive neutrophil heterogeneity in the inflamed gut. We then address the dual role of neutrophils in promoting tissue damage—through cytokine release, immune cell recruitment, ROS production, and NET formation—and in supporting microbial clearance and mucosal healing. We also analyze the molecular mechanisms regulating NETosis, as well as the pathways involved in NET degradation and clearance. Focus is given to the ways in which NETs disrupt the epithelial barrier, remodel the extracellular matrix, contribute to thrombosis, and influence the gut microbiota. Finally, we discuss emerging therapeutic strategies aimed at restoring NET homeostasis—such as PAD4 inhibitors, NADPH oxidase and ROS pathway modulators, and DNase I—while emphasizing the need to preserve antimicrobial host defenses. Understanding neutrophil heterogeneity and NET-related functions may facilitate the development of new therapies and biomarkers for IBD, requiring improved detection tools and integrated multi-omics and clinical data. Full article

The emergence of multidrug-resistant (MDR) bacteria and biofilm-associated infections has created a significant hurdle for conventional antibiotics, prompting the exploration of alternative strategies. Photodynamic therapy (PDT), a technique that utilizes photosensitizers activated by light to produce ROS, has emerged as a beacon of hope in the fight against MDR microorganisms. Among the natural photosensitizers, hypocrellins (A and B) have shown remarkable potential with their dual-mode photodynamic action, generating ROS via both Type I (electron transfer) and Type II (singlet oxygen) pathways. This unique action disrupts bacterial biofilms and inactivates MDR pathogens. The amphiphilic nature of hypocrellins further enhances their promise, enabling deep biofilm penetration and ensuring potent antibacterial effects even in hypoxic environments, surpassing the capabilities of synthetic photosensitizers. This study critically examines the antimicrobial properties of hypocrellin-based PDT, emphasizing its mechanisms, advantages over traditional antibiotics, and effectiveness against MDR pathogens. Comparative analysis with other photosensitizers, the role of nanotechnology-enhanced delivery systems, and future clinical applications are explored. Its combination with nanotechnology enhances therapeutic outcomes, providing a viable alternative to conventional antibiotics. Further clinical research is essential to optimize its application and integration into antimicrobial treatment protocols. Full article

Herpes simplex virus type 1 (HSV-1) is a globally prevalent pathogen that can infect a variety of animal species as well as humans. However, existing antiviral therapies are constrained in their capacity to effectively target viral latency and prevent recurrent infections. Antimicrobial peptides (AMPs), particularly cathelicidins, as part of innate immune system have demonstrated broad-spectrum efficacy against viral pathogens. In this study, four peptides derived from Elephas maximus cathelicidin EM were designed and optimized (EM-1 to EM-4). We identified low toxicity peptide derivatives through hemolytic and cytotoxicity assays, quantified their anti-HSV-1 activity by determining IC₅₀. Antiviral mechanisms were investigated using RT-qPCR and antiviral efficacy was ultimately validated in C57BL/6J mice through viral load quantification in brain, lung, and heart tissues. Our findings revealed that EM-1 significantly inhibited HSV-1 replication in U251 cells. In a murine footpad inoculation model, EM-1 administration substantially reduced viral loads and alleviated inflammatory responses. Histological assessment demonstrated that EM-1 treatment mitigated HSV-1 induced tissue damage in infected mice. We also found that EM-1 exerted its antiviral effects by upregulating the expression of interferon-gamma and its downstream genes, such as ISG15 and MX1. These findings indicated that EM-1 is a dual function peptide that inhibits replication of HSV-1 as well as enhances host antiviral immunity. Collectively, this study highlights the therapeutic potential of elephant cathelicidin derived peptides in antiviral development. Full article

Background/Objectives: Photothermal therapy (PTT) is an emerging minimally invasive strategy in biomedicine that converts near-infrared (NIR) light into localized heat for the targeted inactivation of pathogens and tumor cells. Methods and Results: In this study, we report the synthesis and characterization of thermoresponsive nanogels composed of poly (N-isopropylacrylamide-co-N-isopropylmethylacrylamide) (PNIPAM-co-PNIPMAM) semi-interpenetrated with polypyrrole (PPy), yielding monodisperse particles of 377 nm diameter. Spectroscopic analyses—including ¹H-NMR, FTIR, and UV-Vis—confirmed successful copolymer formation and PPy incorporation, while TEM images revealed uniform spherical morphology. Differential scanning calorimetry established a volumetric phase transition temperature of 38.4 °C, and photothermal assays demonstrated a ΔT ≈ 10 °C upon 10 min of 850 nm NIR irradiation. In vitro antimicrobial activity tests against Pseudomonas aeruginosa (ATCC 15692) showed a dose-time-dependent reduction in bacterial viability, with up to 4 log CFU/mL. Additionally, gentamicin-loaded nanogels achieved 38.7% encapsulation efficiency and exhibited stimulus-responsive drug release exceeding 75% under NIR irradiation. Conclusions: Combined photothermal and antibiotic therapy yielded augmented bacterial killing, underscoring the potential of PPy-interpenetrated nanogels as smart, dual-mode antimicrobials. Full article

Background: Multidrug-resistant (MDR) Escherichia coli (E. coli) strains pose a significant public health challenge, which has led to the exploration of alternative therapeutic strategies. Due to their antibacterial and immunomodulatory properties, bacteriophages have emerged as promising therapeutic agents. Methods: This study investigates the effects of GADS24, a novel lytic bacteriophage of E. coli, on human-monocyte-derived dendritic cells (DCs). DCs are exposed to purified GADS24 phage, bacterial lysate, or a combination of both. Flow cytometry was used to assess the expression of surface markers (HLA-DR, CD80, CD83, and CD86), and ELISA was used to measure cytokine production (IL-10 and IL-12p70). Results: Following treatment with bacterial lysate, a significant increase in DC maturation markers was observed. The GADS24 phage alone induced a moderate upregulation of these markers, decreased IL-10 secretion, and increased IL-12p70. Combining bacterial lysate and phage tempered the maturation response compared to the lysate treatment alone. Conclusion: These findings suggest that GADS24 exerts antibacterial activity and modulates host immunity by influencing DC maturation and cytokine production. Due to its dual antimicrobial and immunomodulatory functions, GADS24 is likely to be a valuable adjunctive therapy for multidrug-resistant (MDR) bacterial infections. Furthermore, in vivo studies are necessary to confirm these promising in vitro results. Full article

Microorganisms play a dual role in human health, serving as both essential allies and serious threats. Their association with infections led to the development of antimicrobials like penicillin, which revolutionized medicine. However, the emergence of antimicrobial resistance (AMR) has created a global health crisis, rendering many treatments ineffective due to pathogen mutations and acquired resistance mechanisms, particularly among ESKAPE pathogens. This resistance increases morbidity, mortality, and healthcare costs, exacerbated by antibiotic overuse and globalization. Biofilms and sepsis further complicate treatment. Addressing AMR requires new therapies, rational antibiotic use, and innovative approaches for drug discovery. Coordinated global action is essential to ensure future access to effective treatments. Antimicrobial peptides (AMPs) derived from Boana species (Anura, Hylidae) represent a promising alternative in the fight against AMR. These peptides exhibit activity against multidrug-resistant pathogens. Unlike conventional antibiotics, Boana peptides act through a broad mechanism that limits resistance development. Their ability to disrupt bacterial membranes and modulate immune responses makes them ideal candidates for the development of new treatments. These peptides may offer valuable alternatives for treating resistant infections and addressing the global AMR crisis. Full article

Although penicillin transformed antibiotic therapy, rising antimicrobial resistance (AMR) has limited its effectiveness, creating a need for new approaches in wound healing. Antimicrobial peptides (AMPs) are promising candidates due to their rapid membrane-disrupting action, immunomodulatory effects, and ability to target drug-resistant pathogens, though their specific roles in promoting wound healing are still not fully understood. This review aims to provide a comprehensive synthesis of the current evidence on the dual role of AMPs as both antimicrobial and immunomodulatory agents in the context of wound healing. Recent studies published between 2020 and 2025 were comprehensively reviewed, focusing on the mechanisms by which AMPs contribute to pathogen elimination, immune regulation, tissue repair, and inflammation resolution. AMPs not only exhibit rapid membrane-disruptive activities against a wide range of pathogens but also influence immune cell behavior, particularly by promoting macrophage polarization toward a reparative M2 phenotype, modulating cytokine and chemokine network, and maintaining T-cell homeostasis. Their ability to simultaneously control infection and regulate inflammation positions AMPs as promising candidates for advanced wound care strategies. The dual antimicrobial and immunomodulatory functions of AMPs represent a synergistic mechanism essential for effective wound recovery. Understanding and harnessing these properties can drive the development of innovative therapies, such as AMP-integrated smart biomaterials and targeted peptide delivery systems, offering new solutions for both acute and chronic wound management. Full article

Pseudomonas aeruginosa is a major pathogen associated with hospital-acquired infections, and the spread of carbapenem-resistant isolates highlights the urgency of developing non-conventional therapies, such as phage therapy. For this alternative to be effective, understanding phage–host interactions is crucial for the selection of candidate phages and offers new insights into these dynamics. Background/Objectives: This study aimed to characterize prophage diversity in clinical P. aeruginosa genomes, assess the relationship between phages and the CRISPR/Cas system, and investigate the potential role of prophages in disseminating resistance genes. Methods: A total of 141 genomes from Brazilian hospitals were analyzed. Prophage detection was performed using VIBRANT, and in silico analyses were conducted to evaluate taxonomic diversity, the presence of resistance genes, phage life cycle, genomic distribution, and the presence of the CRISPR/Cas system. Results: A total of 841 viral sequences were identified by the VIBRANT tool, of which 498 were confirmed by CheckV, with a predominance of the class Caudoviricetes and high overall phage diversity. No statistically significant difference was observed in the number of prophages between isolates with and without CRISPR/Cas systems. Prophages carrying resistance genes such as rsmA, OXA-56, SPM-1, and others were detected in isolates harboring the type I-C CRISPR/Cas system. Additionally, prophages showed no preference for specific insertion sites along the bacterial genome. Conclusions: These findings provide evidence of a well-established phage–host relationship. The dual role of prophages—as vectors of antimicrobial resistance and as potential therapeutic agents—reflects their dynamic impact on bacterial communities and reinforces their importance in developing new strategies to combat antimicrobial resistance. Full article

Sepsis and cancer, though distinct in their clinical manifestations, share profound pathophysiological overlaps that underscore their interconnectedness in disease progression and outcomes. Here we discuss the intricate biological mechanisms linking these two conditions, focusing on the roles of inflammation, immune dysregulation, and metabolic alterations. In sepsis, an uncontrolled immune response to infection leads to a cytokine storm, tissue damage, and immune paralysis, while cancer exploits chronic inflammation and immunosuppressive pathways to promote tumor growth and metastasis. Both conditions exhibit metabolic reprogramming, such as the Warburg effect in cancer and glycolysis-driven immune cell activation in sepsis, which fuels disease progression and complicates treatment. Sepsis can exacerbate cancer progression by inducing genomic instability, epigenetic modifications, and a pro-tumorigenic microenvironment, while cancer increases susceptibility to sepsis through immunosuppression and treatment-related complications. The shared pathways between sepsis and cancer present unique opportunities for therapeutic intervention, including anti-inflammatory agents, immune checkpoint inhibitors, and metabolic modulators. Anti-inflammatory therapies, such as IL-6 and TNF-α inhibitors, show promise in mitigating inflammation, while immune checkpoint inhibitors like anti-PD-1 and anti-CTLA-4 antibodies are being explored to restore immune function in sepsis and enhance antitumor immunity in cancer. Metabolic modulators, including glycolysis and glutaminolysis inhibitors, target the metabolic reprogramming common to both conditions, though their dual roles in normal and pathological processes necessitate careful consideration. Additionally, antimicrobial peptides (AMPs) represent a versatile therapeutic option with their dual antimicrobial and antitumor properties. In this review, we also highlight the critical need for integrated approaches to understanding and managing the complex interactions between sepsis and cancer. By bridging the gap between sepsis and cancer research, this work aims to inspire interdisciplinary collaboration and advance the development of targeted therapies that address the shared mechanisms driving these devastating diseases. Ultimately, these insights may pave the way for novel diagnostic tools and therapeutic strategies to improve outcomes for patients affected by both conditions. Full article

Background/Objective: Antimicrobial resistance (AMR) and therapy-resistant cancer cells represent major clinical challenges, necessitating the development of novel therapeutic strategies. This study explores the use of selenium nanoparticles (SeNPs) and colistin-conjugated selenium nanoparticles (Col-SeNPs) as a dual-function nanotherapeutic against multidrug-resistant Pseudomonas aeruginosa, antifungal-drug-resistant Candida spp., and human breast carcinoma (MCF-7) cells. Methods: SeNPs were synthesized and characterized using UV-Vis spectroscopy, atomic force microscopy (AFM), energy-dispersive X-ray spectroscopy (EDX), X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM), transmission electron microscopy (TEM), and Fourier-transform infrared spectroscopy (FTIR), confirming their nanoscale morphology, purity, and stability. Results: The antimicrobial activity of SeNPs and Col-SeNPs was assessed based on the minimum inhibitory concentration (MIC) and bacterial viability assays. Col-SeNPs exhibited enhanced antibacterial effects against P. aeruginosa, along with significant downregulation of the mexY efflux pump gene, which is associated with colistin resistance. Additionally, Col-SeNPs demonstrated superior antifungal activity against Candida albicans, C. glabrata, and C. krusei compared to SeNPs alone. The anticancer potential of Col-SeNPs was evaluated in MCF-7 cells using the MTT assay, revealing dose-dependent cytotoxicity through apoptosis and oxidative stress pathways. Although MCF-7 is not inherently drug-resistant, this model was used to explore the potential of Col-SeNPs in overcoming resistance mechanisms commonly encountered in cancer therapy. Conclusions: these findings support the promise of Col-SeNPs as a novel approach for addressing both antimicrobial resistance and cancer treatment challenges. Further in vivo studies, including pharmacokinetics and combination therapies, are warranted to advance clinical translation. Full article

Objectives: The synergistic effect of shock wave-enhanced emission photoacoustic streaming (SWEEPS) and antimicrobial photodynamic therapy (aPDT) in mandibular molar root canal disinfection remains underexplored, particularly against dual-species biofilms that better simulate clinical conditions. This study evaluates their combined antimicrobial efficacy against Enterococcus faecalis and Candida albicans biofilms and assesses potential tooth discoloration caused by riboflavin and nano-curcumin. Materials and Methods: The mesiobuccal canals of 57 extracted mandibular molars were inoculated with E. faecalis and C. albicans biofilms. The antimicrobial effects were assessed using riboflavin or nano-curcumin with a 450 nm diode laser (BDL), SWEEPS, or their combinations, compared to 5.25% NaOCl (positive control) and saline (negative control). Biofilm reduction was quantified by colony-forming units (CFUs/mL), and discoloration was evaluated using the ΔE metric in the CIE L*a*b* color space. Results: Both microorganisms showed a significant decrease in colony numbers in all experimental groups compared to the negative control (p < 0.001), except for E. faecalis, where no significant difference was observed between the riboflavin/nano-curcumin groups and the negative control. Combining riboflavin or nano-curcumin with SWEEPS or BDL significantly enhanced antimicrobial efficacy compared to individual treatments (p < 0.001). The combined photodynamic therapy and SWEEPS groups showed the lowest colony counts. The ΔE values were, on average, 1.81 for riboflavin and 1.09 for nano-curcumin. Conclusions: The combination of SWEEPS and aPDT effectively reduces E. faecalis and C. albicans biofilms in molars, supporting its potential as an adjunct in endodontic disinfection. Minimal discoloration further highlights its clinical applicability. Full article

Chronic wounds not only cause significant patient morbidity but also impose a substantial economic burden on the healthcare system. The primary barriers to wound healing include a deficiency of key modulatory factors needed to progress beyond the stalled inflammatory phase and an increased susceptibility to infections. While antimicrobial agents have traditionally been used to treat infections, stem cells have recently emerged as a promising therapy due to their regenerative properties, including the secretion of cytokines and immunomodulators that support wound healing. This study aims to develop an advanced dual-delivery system integrating stem cells and antibiotics. Stem cells have previously been delivered by encapsulation in gelatin methacrylate (GelMA) hydrogels. To explore a more effective delivery method, GelMA was processed into microparticles (MP). Compared to a bulk GelMA hydrogel (HG) encapsulation, GelMA MP supported greater cell growth and enhanced in vitro wound healing activity of human mesenchymal stem cells (hMSCs), likely due to a larger surface area for cell attachment and improved nutrient exchange. To incorporate antimicrobial properties, the broad-spectrum antibiotics penicillin/streptomycin (PS) were loaded into a bulk GelMA hydrogel, which was then cryo-milled into MPs to serve as carriers for hMSCs. To achieve a more sustained antibiotic release, gelatin nanoparticles (NP) were used as carriers for PS. PS was either incorporated during NP synthesis (NP+PS(S)) or absorbed into NP after synthesis (NP+PS(A)). MPs containing PS, NP+PS(S), or NP+PS(A) were tested for their cell carrier functions and antibacterial activities. The incorporation of PS did not compromise the cell-carrying function of MP configurations. The anti-S. aureus activity was detected in conditioned media from MPs for up to eight days—four days longer than from bulk HG containing PS. Notably, the presence of hMSCs prolonged the antimicrobial activity of MPs, suggesting a synergistic effect between stem cells and antibiotics. PS loaded via synthesis (NP+PS(S)) exhibited a delayed initial release, whereas PS loaded via absorption (NP+PS(A)) provided a more immediate release, with potential for sustained delivery. This study demonstrates the feasibility of a dual-delivery system integrating thera Full article

The dynamic development of various branches of medicine and pharmacy, along with the emergence of new preventive and alternative therapies for various diseases, creates opportunities for new solutions utilizing carriers of active substances. Their therapeutic effect may occur through direct contact with skin lesions or indirectly, where medicinal substances penetrate the capillary network in the deeper layers of the skin and reach the bloodstream. The aim of the research was to obtain carriers with a matrix consisting of two renewable-source polymers (chitosan and ethylcellulose) and a core material derived from Ginkgo biloba green leaf extract (GBE). The obtained ethylcellulose microcapsules with encapsulated chitosan nanoparticles with extract {Et[Ch(GB)NP]} were characterized with respect to size, shape, surface morphology (SEM microscopy), and active substance release kinetics (UV-VIS and mathematical release models). The kinetics of active substance release were analyzed using UV-VIS spectroscopy and mathematical release models. The released active components were assessed microbiologically for activity against six bacterial strains and two fungal strains, as well as chromatographically using HPLC-ESI-QTOF-MS/MS fingerprinting. The microcapsules with a dual polymer layer exhibited a slow release of the core material, which demonstrated microbiological activity. The strongest antimicrobial effects were observed against Klebsiella pneumoniae and Salmonella enteritidis, with a minimum inhibitory concentration (MIC) of 410 µg/mL. The release of the core material from the double-layer polymer structures was more efficient in a physiological saline environment, with the best fit for the extract release kinetics following a zero-order model (regression coefficient R² = 0.9939). The obtained microcapsules with a dual polymer layer show great potential for therapeutic applications in the medical industry. Their controlled release properties and antibacterial effectiveness make them a promising carrier for active substances in modern therapies. Full article