Search Results (13,845)

Radiotherapy is a cornerstone of breast cancer treatment, but its efficacy is frequently limited by intrinsic and acquired radioresistance as well as dose-limiting toxicity to surrounding normal tissues. Nanoparticle-mediated radiosensitization has emerged as a promising strategy to enhance the therapeutic index of irradiation by combining physical dose amplification with biological, microenvironmental, and immunological modulation. In this systematic review, we evaluated preclinical evidence on nanoparticle-mediated radiosensitization in breast cancer, with emphasis on nanoplatform design, mechanistic patterns, therapeutic efficacy, and translational relevance. A total of 66 studies published between 2015 and 2026 were included. The identified systems encompassed a broad range of materials, including gold-, silver-, platinum-, bismuth-, gadolinium-, polymer-, lipid-, and hybrid-based nanoplatforms, frequently incorporating targeting ligands, catalytic components, biomimetic coatings, or therapeutic payloads. Enhanced radiation responses were most commonly associated with high-atomic-number (high-Z)-mediated energy deposition, increased reactive oxygen species generation, and enhanced DNA damage persistence. Additional mechanisms, including redox modulation, hypoxia targeting, regulated cell death, and immune activation, reflect the evolution of nanoparticle-assisted radiotherapy from predominantly physical radioenhancement toward multifunctional physicobiological strategies. Triple-negative breast cancer models predominated throughout the literature. Across preclinical models, nanoparticle-assisted irradiation consistently improved clonogenic survival, tumor control, and, in selected studies, survival. However, substantial heterogeneity in study design and limited use of rigorous radiobiological endpoints restricted cross-study comparability. The available preclinical evidence indicates that the most promising nanoparticle-mediated radiosensitization strategies integrate physical dose enhancement with biologically active mechanisms targeting oxidative stress, hypoxia, persistent DNA damage, immune signaling, and tumor microenvironmental resistance. Collectively, these findings suggest that the field is evolving from predominantly physical radioenhancement toward multifunctional, mechanism-driven physicobiological strategies. However, clinical translation remains constrained by methodological heterogeneity and limited radiobiological validation, highlighting the need for standardized preclinical evaluation and clinically feasible nanoplatforms tailored to subtype-specific mechanisms of radioresistance. Full article

The increasing presence of SARS-CoV-2 antivirals (SASs) in wastewater threatens aquatic ecosystems, making it necessary to better understand their removal efficiency during biological treatment. This study evaluates the removal percentages, kinetic mechanisms, and toxicity profiles of six SASs, daclatasvir (DCV), darunavir (DRV), favipiravir (FAV), lopinavir (LOP), remdesivir (REM), and ritonavir (RIT), using activated sludge. A full factorial design combined with response surface methodology (RSM) was used to assess the impact of pH, temperature (T), and mixed liquor suspended solids (MLSS) on SAS removal and microbial stability. The results distinguished two dominant removal pathways. DCV and LOP were primarily removed by adsorption, whereas DRV, FAV, REM and RIT were predominantly removed through biodegradation involving enzymatic transformation and bacterial co-metabolism. RSM achieved a desirability score of 0.772 and identified the optimal operating conditions (pH = 6.08, MLSS = 4.41 g/L, and T = 44.99 °C), resulting in removal efficiencies above 93% for all compounds except DRV, which remained the limiting compound with a maximum removal efficiency of 66%. Perturbation analysis showed that all tested factors have a distinct influence on process performance. These established kinetic trends should support further investigations into advanced biological wastewater treatment methods and precise ecotoxicity profiling of emerging biotransformation products. Full article

Systematic field data on adjuvant-amended microbial-derived pesticides against L. pratensis in arid, high-ultraviolet cotton regions remain scarce. This study systematically evaluated the laboratory toxicity and field efficacy of four kinds of microbial-derived pesticides (abamectin, emamectin benzoate, B. bassiana, and M. anisopliae) and their combinations with adjuvants against L. pratensis in Xinjiang cotton fields. As a comprehensive regional study, this work elucidates the differential enhancement patterns of d-limonene and mineral oil on antibiotic insecticides and entomopathogenic fungi, providing targeted field data for pesticide reduction strategies. The laboratory toxicity of seven microbial-derived pesticides was determined using the leaf-tube residual film method. Four effective agents were selected and combined with d-limonene or mineral oil for field efficacy trials. Abamectin and emamectin benzoate exhibited rapid and high insecticidal activity, with 48 h LC₅₀ values of 1.198 mg/L and 3.424 mg/L, respectively. The two entomopathogenic fungi exhibited slower insecticidal activity than the chemical insecticides but maintained relatively stable control effects throughout the observation period. In field trials, when abamectin or emamectin benzoate was applied at a 30% reduced rate in combination with mineral oil or d-limonene, the control efficacy was equivalent to or higher than that of the full-rate application of the pesticide alone. The treatment of abamectin (4.20 g a.i./hm²) plus mineral oil achieved the highest control efficacy (89.24%) at 3 days post-treatment. For B. bassiana and M. anisopliae, reduced-rate adjuvant-amended treatments showed numerically higher initial and residual efficacy than the full-rate single-agent fungal treatments. The treatment of M. anisopliae (7.35 × 10¹² spores/hm²) plus d-limonene reached 70.50% efficacy at 7 days post-treatment, which was significantly higher than that of the full-rate fungal treatment alone. No phytotoxicity symptoms were observed on cotton plants. Under the tested conditions, the rational combination of microbial-derived pesticides with appropriate adjuvants demonstrates the potential for a 30% reduction in pesticide dosage while maintaining or improving field efficacy, providing region-specific reference for the sustainable management of L. pratensis in Xinjiang cotton fields. Full article

Lung cancer represents a substantial global oncology burden, exhibiting mortality rates that surpass those of prostate, pancreatic, and breast cancers. Extensive research has established a correlation between exposure to polycyclic aromatic hydrocarbon mixtures—particularly those containing benzo(a)pyrene (BaP)—and elevated risks of pulmonary and dermal malignancies across various species, including humans. Hesperidin (HSP), a prominent bioactive flavonoid found in citrus fruits and medicinal herbs such as Hypericum perforatum, is recognized for its diverse pharmacological properties. The present study aimed to elucidate the antioxidant and anti-inflammatory efficacy of HSP against BaP-induced toxicity in the A549 non-small cell lung cancer (NSCLC) cell line. Following the determination of application concentrations via MTT assay, the modulatory effects of HSP on cellular proliferation, oxidative stress markers (TAS, TOS, and OSI), and key pro-inflammatory cytokines (TNF−α, IL−1β, and TGF−β) were systematically evaluated. Isolated exposure to BaP predominantly triggered a targeted upregulation of IL-1β; however, hesperidin demonstrated unexpected pro-oxidant dynamics, characterized by a substantial drop in TAS alongside a concurrent elevation in both TOS and OSI profiles, especially at maximum-dose concentrations. Notably, combining BaP with this heightened hesperidin regimen manifested the most severe oxidative distress phenotype, implying a synergistic pro-oxidant cascade between the two agents. On the contrary, minimized concentrations of hesperidin exerted explicit cytoprotective mitigation against the BaP-induced surge in IL-1β, thereby confirming a highly delicate and narrow therapeutic index for this flavonoid. Full article

Kombucha is a functional beverage produced through the fermentation of Camellia sinensis by a symbiotic culture of bacteria and yeast (SCOBY). Incorporating cashew (Anacardium occidentale L.) and Cajá (Spondias mombin L.) pulps represents a value-addition strategy to mitigate the post-harvest perishability of native Cerrado fruits. This study evaluated physicochemical kinetics, 21-day refrigerated shelf life, consumer acceptance, and biological effects in Caenorhabditis elegans of flavored kombuchas. During a 9-day primary fermentation, the pH decreased to 2.95 while total acidity reached 5.38%. Following flavoring (10% v/v pulp/juice), cashew kombucha exhibited the highest total phenolic content (4.19 mg GAE/mL) and ferric reducing power (FRAP), whereas Cajá kombucha showed superior DPPH scavenging activity (1236 µM TroloxE/mL). Refrigerated storage (4 °C) maintained high counts of viable microorganisms (>10⁵ CFU/mL), though active residual fermentation induced ongoing sugar cleavage and a transient yeast proliferation peak on day 7 (8.15 log CFU/mL in Cajá kombucha). Toxicity assays using C. elegans revealed the initial mortality (31.5–62.5%); however, adjusting the pH to near-neutrality restored high organism viability (<10% mortality), confirming that mortality was acidity-driven. In pH-adjusted media, cashew kombucha promoted a modest extension of nematode lifespan, whereas Cajá kombucha reduced lipid accumulation. Sensory testing revealed moderate consumer acceptance, with cashew kombucha achieving a higher Acceptance Index (72.92%) than Cajá (67.26%). Overall, fruit supplementation enriches the bioactive potential of green tea kombucha, provided that post-fermentation acidity is appropriately managed. Full article

The emergence of antimicrobial resistance necessitates the development of structurally novel agents with improved biological profiles. In this study, a series of new derivatives of fluconazole were designed, synthesized, and evaluated for antifungal activity. The synthetic approach involved esterification of hydroxyl group of fluconazole with an azide-group-containing benzoyl chloride, followed by copper-catalyzed azide–alkyne cycloaddition (CuAAC). The optimized catalytic system was based on a copper(I) catalyst generated from copper(II) palmitate and ascorbic acid. The transformations of the azide-containing derivatives were then performed. The obtained compounds were tested against reference strains of clinically relevant Candida spp., including C. albicans ATCC 10231, C. parapsilosis ATCC 22019, C. krusei ATCC 14243, C. auris CDC B11903, C. tropicalis ATCC 1369, C. glabrata ATCC 15126, and C. lusitaniae ATCC 3449. Some of the obtained derivatives showed very low toxicity in the MTT-based cell viability assay while maintaining high antifungal activity against selected strains. Full article

The demand for sustainable nutrients and bioactive compounds has increased interest in underutilized wild plants. Forestiera tomentosa, a Mexican drupe-bearing species, is largely unexplored. This study evaluated the proximate composition, physicochemical and functional properties, phenolic profile, antioxidant capacity, and toxicological safety of F. tomentosa fruit. The fruit showed high carbohydrate content [71.94% dry weight (DW)], with notable crude fiber (7.90% DW), protein (7.39% DW), and lipid (4.30% DW) contents. Analysis revealed a mildly acidic pH (5.66), titratable acidity of 0.32%, and total soluble solids of 2.33 °Brix. The fruit powder had a low water activity (0.42) and a favorable water solubility index (56.10%), oil absorption (4.54%), and foaming capacity (19.71%). The fruit contained high levels of soluble phenols (280.42 mg GAE/g DW), flavonoids (98.89 mg CE/g DW), anthocyanins (54.53 mg C3G/g DW), and condensed tannins (94.05 mg CE/g DW). High-performance liquid chromatography identified 20 phenolic compounds, with 3-(4-hydroxyphenyl) propionic acid, syringic acid, catechin, epicatechin, and gallocatechin being predominant. The fruit showed significant radical scavenging and reducing potential (DPPH, ABTS, and FRAP). Toxicological evaluation using the Artemia salina bioassay showed a 100% survival rate across all concentrations, indicating no acute toxicity. In silico ADMET predictions revealed favorable pharmacokinetic properties, including high intestinal absorption and compliance with Lipinski’s rule of five. These findings position F. tomentosa as a promising, non-toxic source of functional ingredients for the food, nutraceutical, and pharmaceutical industries, supporting biodiversity conservation and sustainable resource utilization. Further studies are needed to evaluate the potential health benefits of this fruit in vitro and in vivo. Full article

Plasma proteins are becoming more and more popular among researchers due to their minimal toxicity and immunogenicity. The largest percentage of plasma proteins is human serum albumin (HSA). HSA is widely used as a drug carrier due to its biocompatibility and specific affinity to cancer cells. 10H-3,6-diazaphenothiazine (DAPT) is a newly synthesized phenothiazine derivative with promising anticancer activity. The main aim of this study was to encapsulate the DAPT into human serum albumin nanoparticles (DAPT-HSA-NPs) as well as to study DAPT interaction with HSA based on spectroscopic, microscopic, and calorimetric techniques. HSA nanoparticles with DAPT (DAPT-HSA-NPs) were prepared using the desolvation method, and this reaction was accompanied by a thermal transition. High encapsulation efficiency of DAPT into the HSA-NPs (DAPT-HSA-NPs) was obtained (~100%) and its release kinetics from the DAPT-HSA-NP system followed the zero-order kinetic model. Both nanoparticle preparation (HSA-NPs) and HSA interaction with DAPT (DAPT-HSA) resulted in changes in the HSA secondary structure. Moreover, the process of DAPT binding to HSA was exothermic (ΔH [kcal·mol⁻¹] < 0), and DAPT probably formed a static complex with HSA (kq [L·mol⁻¹·s⁻¹] > 10¹²) with moderate affinity (K_a [L·mol⁻¹] of the order of 10⁴). Despite reports on human serum albumin nanoparticles (HSA-NPs) and 10H-3,6-diazaphenothiazine (DAPT), no studies on DAPT encapsulation into HSA-NPs have been published. Therefore, HSA-NPs as a 3,6-diazaphenothiazine delivery system, including preparation methods and interaction analysis, have been evaluated. Full article

Tuberculosis (TB) remains a major global health challenge, compounded by rising drug resistance. Traditional medicinal plants used for TB-related symptoms represent a valuable yet underexplored source of potential antimycobacterial agents. In this study, the phytochemical content and biological activities of Dombeya rotundifolia and Lippia javanica were evaluated, and antimycobacterial compounds were isolated through bioassay-guided fractionation. Plant leaves were collected, extracted with solvents of varying polarity, and screened for phenolics and flavonoids. Antioxidant activity was assessed using DPPH and ferric reducing power assays, antimycobacterial activity was tested against Mycobacterium smegmatis, anti-inflammatory activity was determined by the egg albumin denaturation method, and cytotoxicity was evaluated in THP-1 cells using the MTT assay. Extraction yields varied, with water extracts of L. javanica showing the highest yield and hexane extracts of D. rotundifolia the lowest. Both plants contained bioactive phytochemicals with measurable antioxidant activity, while acetone and dichloromethane extracts of D. rotundifolia displayed the strongest antimycobacterial activity with MIC values of 0.16 mg/mL. Cytotoxicity assays indicated moderate toxicity at higher extract concentrations. Bioassay-guided isolation led to the identification of two fatty acid fractions with tentative characterization, which showed notable antimycobacterial activity (MIC 0.25 mg/mL). These findings provide preliminary support for the ethnomedicinal use of D. rotundifolia in respiratory conditions traditionally associated with tuberculosis and suggest a potential contribution of its fatty acids to its observed antimycobacterial activity. Full article

Dysgeusia is a clinically consequential, but still under-standardized, toxicity of cancer treatment. In the immunotherapy era, taste disturbances are increasingly relevant for patients receiving immune checkpoint inhibitors, chimeric antigen receptor (CAR) T-cell therapies and T-cell-redirecting bispecific antibodies, with G protein-coupled receptor family C group 5 member D (GPRC5D)-directed treatment in multiple myeloma representing a particularly instructive high-burden model. We performed a structured critical narrative review with evidence mapping. PubMed/MEDLINE was searched from database inception to June 2026, complemented by citation tracking in Google Scholar, ClinicalTrials.gov searches and guideline documents relevant to oncology nutrition, oral supportive care and cancer-related taste dysfunction. Search concepts covered cancer-related dysgeusia, immunotherapy-associated oral toxicity, GPRC5D/talquetamab-associated dysgeusia, oncology nutrition, oral–gut microbiome biology, natural taste modulators and miraculin-based interventions. Dysgeusia can reduce appetite, food enjoyment, dietary diversity and protein energy intake, thereby contributing to weight loss, malnutrition risk, distress, social withdrawal and, in severe cases, treatment modification or discontinuation. Available evidence is heterogeneous: general cancer-treatment-associated dysgeusia is supported by broader observational and interventional literature; immunotherapy-associated dysgeusia is less systematically characterized; and GPRC5D/talquetamab-associated dysgeusia represents the most clinically visible and target-specific immunotherapy-associated phenotype. Emerging pilot data suggest that dried miracle berry or miraculin-containing products may improve selected taste perception and nutritional parameters in cancer-related dysgeusia, but direct evidence in immunotherapy-associated dysgeusia is not yet established. We, therefore, propose a claim-disciplined precision supportive-care framework integrating systematic taste phenotyping, early nutritional risk assessment, oral health evaluation, microbiome-aware but hypothesis-generating endpoints, individualized flavor and texture adaptation, cautious use of natural taste modulators in selected patients and iterative monitoring of patient-centered outcomes. Future trials should test whether dysgeusia-focused nutritional and taste-modulating supportive care interventions can improve intake, quality of life and treatment persistence without compromising immunotherapy safety or efficacy. Full article

Toxoplasmosis remains a major global health concern, particularly in immunocompromised individuals and pregnant women, while currently available therapies are associated with significant toxicity and limited efficacy against chronic infection. Drug repurposing represents an attractive strategy for the identification of safer and more effective anti-Toxoplasma gondii agents. This study investigated the antiparasitic potential of loratadine, a second-generation antihistamine, using an integrated in silico, in vitro, and in vivo approach. The anti-T. gondii activity of loratadine was evaluated through β-galactosidase-based proliferation assays, reversibility assays, and experiments using pretreated tachyzoites. In vivo efficacy was assessed in murine models of acute and chronic toxoplasmosis. Disease progression, survival, parasite burden, and cerebral cyst formation were analyzed following treatment. Loratadine inhibited the intracellular proliferation of T. gondii tachyzoites in a concentration-dependent manner and induced partially irreversible effects on parasite viability after drug withdrawal. Pretreatment of extracellular tachyzoites produced limited effects, suggesting that loratadine predominantly acts during the intracellular stage of infection. In the acute toxoplasmosis model, loratadine treatment delayed disease progression, prolonged animal survival, and significantly reduced the number of tachyzoites recovered from the peritoneal cavity. In the chronic infection model, treatment significantly decreased both the number and size of cerebral cysts, although these findings do not demonstrate cyst eradication or direct bradyzoite killing. Despite its measurable biological activity, loratadine exhibited a relatively low in vitro selectivity index, highlighting the need for further optimization. These exploratory findings identify loratadine as a promising lead compound (hit) for further optimization rather than an immediately translatable therapeutic candidate. Additional medicinal chemistry, pharmacokinetic, mechanistic, and confirmatory preclinical studies will be required to determine its potential for anti-T. gondii drug development. Full article

Background/Objectives: Cisplatin-induced testicular toxicity is commonly associated with oxidative stress; however, the early biological events preceding overt tissue injury remain incompletely characterized. Identifying interventions capable of preserving redox homeostasis during this subacute phase may improve our understanding of the initial mechanisms underlying testicular dysfunction. This study investigated whether methylsulfonylmethane (MSM), a naturally occurring organosulfur compound with antioxidant properties, modulates early oxidative responses in a subacute rat model of cisplatin-induced testicular toxicity. Methods: Thirty-two adult male Sprague–Dawley rats were randomly assigned to Control, Cisplatin (CIS), MSM, and CIS + MSM groups (n = 8/group). MSM (500 mg/kg/day, intraperitoneally) was administered for 10 consecutive days, while a single dose of cisplatin (7 mg/kg, intraperitoneally) was given on day 7. Oxidative stress biomarkers, antioxidant enzyme activities, intratesticular testosterone concentrations, inflammatory cytokines, GPX4 and HO-1 protein expression, histopathological alterations, and correlation analyses were evaluated. Results: Cisplatin exposure induced a marked oxidative imbalance, evidenced by increased malondialdehyde levels and reduced superoxide dismutase, catalase, glutathione peroxidase, and intratesticular testosterone concentrations (p < 0.05). MSM administration attenuated lipid peroxidation, restored antioxidant enzyme activities, and preserved intratesticular testosterone levels. Western blot analysis demonstrated a significant increase in GPX4 protein expression following cisplatin exposure, whereas MSM normalized GPX4 expression toward control values. In contrast, HO-1 expression and intratesticular IL-6 and TNF-α levels did not differ among the experimental groups. Histopathological evaluation revealed only mild structural alterations without corresponding differences in Johnsen score, indicating that biochemical and molecular disturbances preceded overt tissue degeneration. Correlation analysis further demonstrated close associations between antioxidant defense and preservation of endocrine function. Conclusions: Subacute cisplatin exposure primarily disrupted testicular redox homeostasis before prominent histopathological injury became evident. MSM was associated with attenuation of these early oxidative alterations accompanied by improved endogenous antioxidant enzyme activity, higher intratesticular testosterone concentrations, and normalization of GPX4 expression. These findings suggest that MSM may contribute to the maintenance of testicular redox homeostasis during the early phase of cisplatin-induced toxicity under the present experimental conditions. Full article

Background and Clinical Significance: Enfortumab vedotin combined with pembrolizumab has emerged as an effective first-line therapy for advanced urothelial carcinoma. While immune checkpoint inhibitors are associated with digestive tract toxicities, upper gastrointestinal involvement such as esophagitis remains rare, and its presentation in combination with enfortumab vedotin is not well characterized. Case Presentation: A 72-year-old man with metastatic urothelial carcinoma presented with generalized weakness, poor oral intake, odynophagia, dysphagia, anemia, and systemic symptoms following the second cycle of combination therapy of enfortumab vedotin and pembrolizumab. Endoscopic evaluation revealed diffuse circumferential ulcerative esophagitis involving the entire esophagus, with associated duodenitis. Infectious workup, including Clostridioides difficile, cytomegalovirus, and human immunodeficiency virus testing, was negative, and HSV-1 IgG was positive, consistent with prior exposure rather than active infection; however, tissue-based testing for active HSV infection was not performed. Lower gastrointestinal evaluation demonstrated nonspecific rectal inflammation. The patient was treated with high-dose intravenous corticosteroids (intravenous methylprednisolone 1 mg/kg/day) with rapid clinical improvement within 48–72 h, followed by a steroid taper and supportive care. Conclusions: This case represents a severe and diffuse manifestation of esophagitis associated with enfortumab vedotin and pembrolizumab therapy. While immune-mediated esophagitis is rare, the combination of antibody–drug conjugate therapy with immune checkpoint inhibition may contribute to synergistic mucosal injury. Early recognition and prompt initiation of immunosuppressive therapy are critical for favorable outcomes. Clinicians should be aware of severe esophagitis as a potential complication of enfortumab vedotin and pembrolizumab therapy. Timely diagnosis and management with corticosteroids can lead to rapid symptom resolution and may prevent serious complications. Full article

2-phenylbenzimidazole-5-sulfonic acid (PBSA) is a commonly used organic ultraviolet (UV) filter frequently found in aquatic environments, raising substantial ecological health concerns. While some toxic effects of PBSA on aquatic organisms have been reported, its intergenerational developmental and neurotoxic risks remain poorly understood. In this study, we established a zebrafish life-cycle exposure model to explore the intergenerational toxicity of environmentally relevant concentrations of PBSA (0.2, 2, and 20 μg/L). Offspring were categorized into three exposure groups: parental exposure only (F0+/F1−), parental exposure with continuous F1 exposure (F0+/F1+), and only F1 exposure without parental treatment (F0−/F1+). Our findings demonstrate the transfer of PBSA from parental gonads to F1 embryos. Parental lifetime exposure significantly inhibited somitogenesis and increased mortality and malformation rates in the F1 generation, with the most pronounced developmental damage observed in the F0+/F1+ group. Whole-mount immunohistochemistry revealed that PBSA notably reduced motor neuron axon length in F1 larvae, accompanied by downregulation of developmental-related genes including gap43, mbp, and shha. Mechanistically, the F0+/F1− group exhibited a marked increase in MDA levels. Excessive ROS accumulation and reduced CAT activity were specifically observed in the F0+/F1+ group, whereas the F0+/F1− and F0−/F1+ groups showed significantly elevated CAT activity, jointly driving developmental and neurotoxic changes. In silico predictions indicated low acute aquatic toxicity of PBSA, contradicting its observed intergenerational risks. Our findings demonstrate that parental lifetime PBSA exposure can induce significant intergenerational neurodevelopmental toxicity in zebrafish offspring by disrupting oxidative balance and neural gene expression, with continuous offspring exposure further aggravating the adverse effects. This research underscores that traditional single-generation toxicity assessments underestimate the ecological dangers of UV filters. It also offers new insights into the environmental risk evaluation of PBSA and similar emerging contaminants. Full article

Conventional antibiotics exhibit limited ability to penetrate host cell membranes, making intracellular bacterial infections difficult to eradicate completely. As naturally derived nanoscale membrane structures, bacterial extracellular vesicles (EVs) possess excellent biocompatibility and intrinsic transmembrane transport capability, thereby demonstrating unique advantages for in vivo drug delivery. The present study investigated the feasibility of using EVs derived from the avirulent Streptococcus suis T15 as novel carriers for ciprofloxacin delivery. We also comprehensively evaluated the biosafety and anti-infective efficacy of this nanodrug delivery system in vitro and in vivo. Cytotoxicity assays, live/dead cell staining, and hemolysis analyses demonstrated that T15-derived EVs at concentrations below 50 μg/mL did not cause significant cellular damage or hemolysis. Serum biochemical analyses in mice further confirmed the absence of obvious organ toxicity, indicating favorable biosafety within the tested concentration range. Ciprofloxacin was successfully loaded into EVs using a combination of ultrasonication and electroporation, achieving a drug concentration of 438.6 μg/mL and a loading efficiency of 10.96%. The ciprofloxacin-loaded EVs (EV-CIP) exhibited significantly greater antibacterial activity than free ciprofloxacin against both intracellular bacteria and fluoroquinolone-resistant strains exhibiting efflux pump activity. Evaluation in animal infection models showed that EV-CIP markedly reduced mortality in infected Galleria mellonella larvae. It also decreased bacterial burdens in multiple mouse organs and significantly alleviated histopathological damage. These results collectively suggest that EVs derived from the avirulent S. suis T15 were safe and effective within the tested concentration range and experimental conditions. The EV-based ciprofloxacin delivery system substantially enhanced the clearance of intracellular pathogens and fluoroquinolone efflux pump-positive bacteria, suggesting its potential application in the treatment of difficult-to-treat bacterial infections. This study provides a theoretical and experimental basis for the further development of novel EV-based anti-infective drug delivery strategies for livestock and poultry. Full article