Poisoning Research Articles

Ecological risk evaluation of spent engine oil pollution using earthworm and microbial bioassays

The study aimed to assess the ecotoxicological risk associated with the indiscriminate disposal of spent engine oil on terrestrial ecosystem using earthworm and microbial assays. Soil samples were collected from a depth of 0-20 cm and subjected to standard analytical protocols for analysis. Earthworms (assessed by mortality rate) and microorganisms (evaluated for inhibitory effects) covered a wide range of short-term lethal and sub-lethal endpoints used for risk characterization, analyzed through Probit analysis. The result of acute toxicity assay revealed that microbial absorbance rated depended on the dose and type of organism, ranking in the order: Acinetobacter > Enterobacter > Bacillus species >Pseudomonas. Aas oil concentratoin increase, mortality among earthworm was observed. Risk Quotient (RQ) values for Zea mays, Vigna unguiculata, Glycine max and earthworm varied from low to very high risk based on estimated Predicted No Effect Concentration (PNEC) values. Microorganisms exhibited differing level of biotolerance to spent engine oil exposure as indicated by respective risk quotient values. Exposure to spent engine oil posed minimal risk to Pseudomonas sp., Bacillus sp., and Acinetobacter sp., with RQ values below unity (< 1). Conversely, Enterobacter sp. Showed a high risk with values above unity. Earthworms play a pivotal role in agriculture due to their numerous economic benefots. Soil microorganisms are essential for maintening soil quality by performing vital processes. The antimicrobial properties of spent engine oil on soil may distort microbial activities, potentially inhibiting their growth and leading to alterations in ecological functionality of the soil.

Anti-inflammatory and antinociceptive effects, toxicity, and phytochemical analysis of Beaumontia grandiflora Wall.

Preliminary pharmacological studies revealed that the EtOAc fraction (BGEA) might be the main active fraction with anti-inflammatory and antinociceptive effects in Beaumontia grandiflora Wall. Further assays on BGEA at doses of 200, 400, and 800 mg/kg using four animal models showed that it could inhibit the xylene-induced ear edema, carrageenan-induced paw edema, and acetic acid-induced writhing and prolong the latency time in the hot-plate test. ELISA analysis revealed that the anti-inflammatory activity of BGEA might be associated with the decrease of TNF-α, IL-1β, and IL-6 levels and the increase of the IL-10 level. The acute toxicity test showed that except for the n-BuOH fraction, the LD50 values of the extract and other three fractions were higher than 2000 mg/kg bw. Finally, 14 compounds were identified from BGEA by LC-MS. This research provides some basis for the folk use of B. grandiflora in the treatment of inflammation and pain-related diseases.

Phytochemical composition and safety of Vernonia Amygdalina ethanolic extract with anti-colon cancer properties

This study evaluates the therapeutic efficacy and safety of Vernonia Amygdalina extract (VAEE) in treating colorectal cancer (CRC) induced by azoxymethane/dextran sulfate sodium (AOM/DSS) in mice and to elucidate the underlying mechanisms. The study utilized a mouse model of CRC to assess the impact of VAEE on pathological markers, inflammatory mediators, and oxidative stress. Phytochemical profiling of VAEE was conducted using LC-HRMS, focusing on phenolic compounds. The extract's antioxidant activity was quantified, and its safety profile was verified through acute toxicity assessments. VAEE significantly mitigated the AOM/DSS-induced reduction in colon length and weight loss in a dose-dependent manner. The treatment decreased pro-inflammatory cytokines (IL-6, IL-1β, TNF-α) while increasing the anti-inflammatory cytokine IL-10. VAEE also demonstrated strong antioxidant activity and did not adversely affect blood, kidney, or liver biomarkers, confirming its non-toxicity. Protein-protein interaction analysis suggested VAEE's role in inhibiting inflammatory markers, including COX-2, IL-18, and NF-kB. Molecular docking results supported the extract's affinity for these proteins, indicating potential as a COX-2 inhibitor. VAEE exhibits potent anti-inflammatory, antioxidative, and anticarcinogenic properties against CRC, with a favorable safety profile. These findings advocate for the integration of VAEE as a novel therapeutic agent in CRC treatment. Further investigations into its molecular mechanisms and long-term effects are warranted to facilitate clinical translation.

Success of Ultra-low Dose Radiation Therapy for Primary Cutaneous B-cell Lymphoma.

Primary cutaneous B-cell lymphoma (PCBCL) is a relatively rare disease, associated with 5-year overall survival of nearly 95% when treated with external beam radiation therapy (EBRT) alone. However, standard EBRT doses yield acute skin toxicity in more than 70% of patients and grade 3 to 4 acute skin toxicity in nearly 10% of patients. Consequently, the PCBCL treatment paradigm is shifting towards lower EBRT doses. This study evaluates our early experience with ultra-low dose EBRT (total dose of 4 Gy in 2 fractions) for PCBCL. Four biopsy-confirmed PCBCL lesions (1 anterior thigh and 3 chest) in 2 male patients were treated with 2 Gy×2 fraction EBRT using electrons through a clinical setup. The anterior thigh lesion was treated using a clamshell to protect the scrotum from scatter dose. Treatment was achieved using 9 MeV electrons to the 85% isodose line using no bolus, with follow-up every 4 months and potential retreatment if no visible response at 8 to 9 months. All lesions demonstrated a response to EBRT by 4 months, visibly manifesting as flattening with changes in pigmentation. At the last follow-up (20, 20, 16.5, and 4 mo, respectively), all lesions had flattened with no evidence of local recurrence and no skin toxicity. Treatment of PCBCL with ultra-low dose EBRT to 4 Gy total dose in 2 fractions provides durable local control with zero skin toxicity. These results are encouraging for both the success of treatment and the potential to use similarly low doses for retreatment should patients exhibit local recurrence.

Radiation enhancement using focussed ultrasound-stimulated microbubbles for breast cancer: A Phase 1 clinical trial.

Preclinical studies have demonstrated that tumour cell death can be enhanced 10- to 40-fold when radiotherapy is combined with focussed ultrasound-stimulated microbubble (FUS-MB) treatment. The acoustic exposure of microbubbles (intravascular gas microspheres) within the target volume causes bubble cavitation, which induces perturbation of tumour vasculature and activates endothelial cell apoptotic pathways responsible for the ablative effect of stereotactic body radiotherapy. Subsequent irradiation of a microbubble-sensitised tumour causes rapid increased tumour death. The study here presents the mature safety and efficacy outcomes of magnetic resonance (MR)-guided FUS-MB (MRgFUS-MB) treatment, a radioenhancement therapy for breast cancer. This prospective, single-center, single-arm Phase 1 clinical trial included patients with stages I-IV breast cancer with in situ tumours for whom breast or chest wall radiotherapy was deemed adequate by a multidisciplinary team (clinicaltrials.gov identifier: NCT04431674). Patients were excluded if they had contraindications for contrast-enhanced MR or microbubble administration. Patients underwent 2 to 3 MRgFUS-MB treatments throughout radiotherapy. An MR-coupled focussed ultrasound device operating at 800 kHz and 570 kPa peak negative pressure was used to sonicate intravenously administrated microbubbles within the MR-guided target volume. The primary outcome was acute toxicity per Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Secondary outcomes were tumour response at 3 months and local control (LC). A total of 21 female patients presenting with 23 primary breast tumours were enrolled and allocated to intervention between August/2020 and November/2022. Three patients subsequently withdrew consent and, therefore, 18 patients with 20 tumours were included in the safety and LC analyses. Two patients died due to progressive metastatic disease before 3 months following treatment completion and were excluded from the tumour response analysis. The prescribed radiation doses were 20 Gy/5 fractions (40%, n = 8/20), 30 to 35 Gy/5 fractions (35%, n = 7/20), 30 to 40 Gy/10 fractions (15%, n = 3/20), and 66 Gy/33 fractions (10%, n = 2/20). The median follow-up was 9 months (range, 0.3 to 29). Radiation dermatitis was the most common acute toxicity (Grade 1 in 16/20, Grade 2 in 1/20, and Grade 3 in 2/20). One patient developed grade 1 allergic reaction possibly related to microbubbles administration. At 3 months, 18 tumours were evaluated for response: 9 exhibited complete response (50%, n = 9/18), 6 partial response (33%, n = 6/18), 2 stable disease (11%, n = 2/18), and 1 progressive disease (6%, n = 1/18). Further follow-up of responses indicated that the 6-, 12-, and 24-month LC rates were 94% (95% confidence interval [CI] [84%, 100%]), 88% (95% CI [75%, 100%]), and 76% (95% CI [54%, 100%]), respectively. The study's limitations include variable tumour sizes and dose fractionation regimens and the anticipated small sample size typical for a Phase 1 clinical trial. MRgFUS-MB is an innovative radioenhancement therapy associated with a safe profile, potentially promising responses, and durable LC. These results warrant validation in Phase 2 clinical trials. clinicaltrials.gov, identifier NCT04431674.

Assessment of the Hazard and Ecotoxicity of the Residues of Paiche Leather Dyed with Natural and Synthetic Colourants: A Focus on Environmental Sustainability

The aim of this research was to assess the hazardousness and ecotoxicity of paiche leather (Arapaima gigas) dyed with natural colourants (turmeric and purple corn) versus synthetic colourants (anilines). To determine hazardousness, the methodology included the assessment of flammability, corrosivity, reactivity to H2S and HCN, toxicity from metals, and organic compounds of dyed leather. Additionally, its ecotoxicity was determined using the California red worm (Eisenia fetida) as a bioindicator through a bioassay, with treatments at 0.02, 0.04, 0.08, 0.16, and 0.20 g of leather/g of substrate, including undyed leather and a negative control in the investigation. The hazardousness analysis results indicated that leather samples dyed with both natural and synthetic colourants are not hazardous. However, the concentrations of chromium, nickel, cadmium, and lead exceed the permitted values for their use in footwear according to the European Union. Regarding ecotoxicity, the results demonstrate that acute toxicity to E. fetida is lower for natural colourants compared to synthetic colourants, where 100% mortality occurs at concentrations between 0.04 and 0.08 g of leather/g of the substrate. Concerning chronic toxicity, after 12 weeks of exposure, the tolerance concentration for undyed paiche leather is 0.035 g of leather/g of the substrate, and for leather dyed with purple corn and turmeric, it is 0.2 g of leather/g of the substrate. It is shown that the active compounds of natural colourants have a positive effect on worm survival, and it is concluded that paiche leather dyed with these colourants presents environmental advantages over leather dyed with synthetic colourants.

Bisphenol S exposed changes in intestinal microflora and metabolomics of freshwater crayfish, Procambarus clarkii

Bisphenol S (BPS), a typical endocrine-disrupting chemical (EDC), can cause hepatopancreas damage and intestinal flora disturbance. Comprehensive studies on the mechanisms of acute toxicity in crustaceans are lacking. In this study, 16S rRNA and liquid chromatography were used to investigate intestinal microbiota and metabolites of freshwater crayfish (Procambarus clarkii). In this study, freshwater crayfish were exposed to BPS (10 µg/L and 100 µg/L). The results showed a significant decrease in catalase (CAT) and superoxide dismutase (SOD) activities after exposure to BPS, which inhibited the Nrf2-Keap1 signaling pathway and induced oxidative stress toxicity in freshwater crayfish. In addition, BPS exposure induced the structural changes of intestinal microbial in the freshwater crayfish, showing different patterns of effects. The number of potentially pathogenic bacteria increased, such as Citrobacter, Hafnia-Obesumbacterium, and RsaHf231. A total of 128 different metabolites were analyzed by LC-MS/MS. The inositol and leukotriene (LT) contents in the hepatopancreas of freshwater crayfish were significantly decreased after 10 µg/L BPS exposure, which in turn led to the accumulation of lipids causing hepatopancreas damage. In conclusion, when the concentration of BPS in the water environment exceeded 10 µg/L, the freshwater crayfish intestinal microbiota was dysbiosis and the hepatopancreas metabolism was disturbed.

Cell based and In vivo systematic evaluation of some Egyptian plant extracts targeting breast cancer

The prevalence of breast cancer as a significant public health concern necessitates continued exploration of natural resources for novel anti-cancer agents is crucial. Material and methodsAnticancer activity of plant extracts on monolayer breast cancer cell line (MCF7) with lower levels of toxicity towards normal (RPE1) underwent further assessment using a three-dimensional model (3D). The extract's effects were investigated through multiple assays including apoptosis induction using quantifying cleaved cytokeratin-18 (CK18) and DNA fragmentation. Additionally, the expression of Bcl-2 and Bax was quantitative using real-time PCR. The median lethal dose (LD50) was determined by the acute oral toxicity, while biomarkers associated with tumorigenesis, metastasis, and cell death were quantified by ELISA. ResultsLimoniastrum monopetalum and Bauhinia variegata exhibited the most potent antitumor efficacy among the investigated extracts. They demonstrated potent cytotoxicity against MCF7 with no significant effect on hTERT RPE-1, with an IC50 of 100 μM. The extract demonstrated effectiveness in killing cancer cells within 3D tumor-like structures, induced apoptosis through caspase-3 activation and cleavage of cytokeratin-18, up-regulated the tumor suppressor p53, down-regulated the anti-apoptotic Bcl-2 gene, and caused DNA fragmentation. Acute oral toxicity studies in mice indicated low toxicity, and in a syngeneic mouse tumor model, the extract significantly inhibited tumor growth, suggesting its potential for further development. ConclusionLimoniastrum monopetalum and Bauhinia variegata exhibited the most potent antitumor efficacy among the investigated extracts.

LINAC–BASED STEREOTACTIC ARRHYTHMIA RADIOABLATION (STAR) FOR PAROXYSMAL ATRIAL FIBRILLATION IN ELDERLY: A PROSPECTIVE PHASE II TRIAL

Abstract Background and Aims The aim of this trial is to investigate the feasibility of radiotherapy for the treatment of paroxysmal atrial fibrillation (AF) in elderly patients. Method inclusion criteria were: age > 70 years, symptomatic AF, antiarrhythmic drugs failure or intolerance. All patients underwent to 4D cardiac Computed Tomography simulation. The clinical target volume was identified in the area around pulmonary veins (PV). STAR was performed with a total dose of 25 Gy (single fraction) delivered in 3 minutes. Results Twenty patients were enrolled and 18 underwent STAR. One patient withdrew informed consent before treatment and 1 patient was excluded due to unfavorable esophagus position. With a median follow–up (FU) of 16 months (range 12–23), no acute toxicity more than grade 3 was reported. Five patients had a grade 1 esophagitis 24 hours after STAR; eight patients had an asymptomatic grade 1 pericardial effusion, one patient had a torsade de pointes treated effectively by electrical cardioversion and subsequent cardiac ICD implantation. Most patients had a significant reduction in AF episodes. Five patients, due to arrhythmias recurrences after STAR, performed electrophysiological study documenting successful PV isolation. Finally, a significant improvement of quality of life was documented (48 ± 15 at enrollment vs 75 ± 15 at 12 months FU; p < 0.001). Conclusion The present phase II trial demonstrated the feasibility of STAR in paroxysmal AF elderly patients and its potential role in increasing the quality of life. Surely, more robust data are needed about safety and efficacy.

Current scenario of fused pyrimidines with in vivo anticancer therapeutic potential.

Cancer, characterized by uncontrolled cell growth and metastasis, is responsible for nearly one in six deaths and represents a severe threat to public health worldwide. Chemotherapy can substantially improve the quality of life and survival of patients with cancer, but anticancer chemotherapeutics are associated with a range of adverse effects. Moreover, almost all currently available anticancer chemotherapeutics could develop drug resistance over a period of time of application in cancer patients and ultimately lead to cancer relapse and death in 90% of patients, creating an urgent need to develop new anticancer agents. Fused pyrimidines trait the inextricable part of DNA and RNA and are vital in numerous biological processes. Fused pyrimidines can act on various biological cancer targets and have the potential to address drug resistance. In addition, more than 20 fused pyrimidines have already been approved for clinical treatment of different cancers and occupy a prominent place in the current therapeutic arsenal, revealing that fused pyrimidines are privileged scaffolds for the development of novel anticancer chemotherapeutics. The purpose of this review is to summarize the current scenario of fused pyrimidines with in vivo anticancer therapeutic potential along with their acute toxicity, metabolic profiles as well as pharmacokinetic properties, toxicity and mechanisms of action developed from 2020 to the present to facilitate further rational exploitation of more effective candidates.

STUDY OF ACUTE AND SUB-ACUTE TOXICITY OF A MEDICATION BASED ON SPIDER VENOM EXTRACT

Homeopathy is a regulatory therapy. The effectiveness of homeopathic therapy does not depend on the dose of the drug, but on the frequency of its repetitions. The composition of homeopathic preparations includes a wide range of natural and synthetic active substances: minerals; chemical substances; substances of plant origin; microorganisms, including fungi, bacteria, viruses, and plant parasites; substances of animal origin; and human materials, which may include tissues, secretions, hormones, and genetically homogeneous cell lines. One such substance is an extract of spider venom (Tarantul cubensis D6), which remains active in pharmaceutical preparation for a long time. The drug is selectively absorbed in inflamed tissues, differentiating them from healthy cells and suppressing inflammation. The drug is also effective in necrotic and proliferative processes. It is used for the treatment of panaritium in the initial stage, skin ulcers, necrobacillosis, and necrosis of the soft tissues of the animal. Any materials of animal or human origin are potentially dangerous for human and animal health, as they may contain toxic or pathogenic substances. Therefore, the study of the acute and subacute toxicity of spider venom extract is one of the stages of establishing the toxicological parameters of the drug. The use of the drug in a therapeutic dose caused an increase in animal body weight, hemoglobin concentration, number of leukocytes, erythrocytes, hematocrit value, average erythrocyte volume (MCV), average hemoglobin content in erythrocytes (МСН), average concentration of hemoglobin in erythrocytes (МСНС), number of platelets, and AST activity against the background of a slight decrease in total protein content, creatinine, urea, and ALT activity. The use of the drug in a 10-fold therapeutic dose caused an increase in animal body weight, creatinine, urea, ALT, and AST activity against the background of a decrease in the concentration of hemoglobin, the number of leukocytes and erythrocytes, the value of hematocrit, the average volume of erythrocytes (MCV), the average content of hemoglobin in erythrocytes (МСН), the average concentration of hemoglobin in erythrocytes (МСНС), the number of platelets, and the content of total protein.

Daphnia magna model for the study of mycotoxins present in food: Gliotoxin, ochratoxin A and its combination

Mycotoxins are low molecular weight compounds present in food and feed. Although their effects on human health have been widely described, their mechanisms of action are still undefined. Gliotoxin (GTX) and ochratoxin A (OTA) are among the most dangerous mycotoxins produced by Aspergillus spp. Therefore, their toxicity was studied in the Daphnia magna model, which has high capacity to predict cytotoxicity and assess ecotoxicity, comparable to mammalian models. The study consisted of a series of tests to evaluate the effects of mycotoxins GTX, OTA and their combinations at different dilutions on Daphnia magna that were conducted according to standardized OECD 202 and 211 guidelines. The following assays were carried out: acute toxicity test, heartbeat, delayed toxicity test, reproduction, growth rate test. Reproducibility was determined by observing the offspring after 21 days of GTX exposure. In acute and delayed toxicity transcript levels of genes involved in xenobiotic metabolism (mox, gst, abcb1, and abcc5), and oxidative stress (vtg-SOD) were analyzed by qPCR. GTX showed acute toxicity and decreased heart rate in D. magna compared to OTA. On the other hand, OTA showed a delayed effect as evidenced by the immobility test. Both mycotoxins showed to increase genes involved in xenobiotic metabolism, while only the mycotoxin mixture increased oxidative stress. These results suggest that the mycotoxins tested could have negative impact on the environment and human health.

Exploring structure/property relationships to health and environmental hazards of polymeric polyisocyanate prepolymer substances-3. Aquatic exposure and hazard of aliphatic diisocyanate-based prepolymers.

The water extractability and acute aquatic toxicity of seven aliphatic diisocyanate-based prepolymer substances were investigated to determine if lesser reactivity of the aliphatic isocyanate groups, as well as increased ionization potential of the expected (aliphatic amine-terminated) polymeric hydrolysis products, would influence their aquatic behavior compared to that of previously investigated aromatic diisocyanate-based prepolymers. At loading rates of 100 and 1,000mg/L, only the substances having log Kow ≤9 exhibited more than 1% extractability in water, and a maximum of 66% water extractability was determined for a prepolymer having log Kow = 2.2. For the more hydrophobic prepolymer substances (log Kow values from 18-37), water extractability was negligible. High-resolution mass spectrometric analyses were performed on the water-accommodated fractions (WAF) of the prepolymers, which indicated the occurrence of primary aliphatic amine-terminated polymer species having backbones and functional group equivalent weights aligned to those of the parent prepolymers. Measurements of reduced surface tension and presence of suspended micelles in the WAFs further supported the occurrence of these surface-active cationic polymer species as hydrolysis products of the prepolymers. Despite these characteristics, the water-extractable hydrolysis products were practically non-toxic to Daphnia magna. All of the substances tested exhibited 48-h EL50 values of >1,000mg/L, with one exception of EL50 = 157mg/L. The results from this investigation support a grouping of the aliphatic diisocyanate-based prepolymers as a class of water-reactive polymer substances having predictable aquatic exposure and a uniformly low hazard potential, consistent with that previously demonstrated for the aromatic diisocyanate-based prepolymers.

Acute and multigenerational toxicity of polylactic acid microplastics on a copepod bioindicator

Acute and multigenerational toxicity of polylactic acid microplastics on a copepod bioindicator

AN ASSESSMENT OF PESTICIDE POISONING INCIDENCES PRESENTED AT HEALTH CARE FACILITIES IN MASHONALAND CENTRAL PROVINCE, ZIMBABWE

Acute Pesticide Poisoning (APP) is a significant problem in developing countries, causing loss of productivity and fatalities in the agricultural sector. However, limited information on the connection between pesticide use, APP, and deaths in Zimbabwe is available. This study aimed to evaluate incidents that resulted in APP and identify the specific pesticides that caused them at Health Care Facilities (HCFs) in Mashonaland Central Province. Researchers conducted a survey asking standardized questions to gather information on APP cases from 93 HCFs. Descriptive statistics and chi-square association tests for APP cases in the targeted HCFs were calculated using IBM SPSS version 22. The study found that 43% of APP cases were due to pesticides belonging to the World Health Organization (WHO) class II acute toxicity category, while 26.1% were caused by Highly Hazardous Pesticides (HHPs). Most of the cases were due to intentional poisoning (87.1%), with the majority (55.9%) of APP incidents being males. The highest APP cases were recorded in the 21-30 age group (38.8%), followed by the 31-40 age group (32.8%). These results emphasize the significant impact of intentional poisoning by WHO class II type pesticides, particularly HHPs, on the incidence of APP in Zimbabwe. To mitigate the impact of HHPs on human health, it is recommended that the government of Zimbabwe consider pesticide risk reduction measures, such as stricter pesticide registration criteria, import restrictions, and the promotion of less toxic alternatives. These findings highlight the urgent need for policymakers, researchers, and other stakeholders in the agricultural sector to work collaboratively towards creating a safer and more sustainable farming environment in Zimbabwe.

Patterns and clinical outcomes of childhood poisoning presenting to a children’s emergency department in Yenagoa, Nigeria: a 10-year retrospective study

IntroductionBackground: Childhood poisoning, characterised by exposure to toxic substances, poses a global health concern with variations across regions. Despite the importance of having current information about childhood acute poisoning in...

Acute toxicity and anti-inflammatory activity of bis-thiourea derivatives

Abstract In the current work, bis-thiourea derivatives have been synthesized through condensation reaction between isothiocynates and diamines in dry acetone to form SK1 (1,2-bis(N-benzoylthioureido) benzene), SK2 (1,3-bis(N-benzoylthioureido) benzene), and SK3 (1,4-bis(N-benzoylthioureido) benzene). The structures of new synthesized derivatives were confirmed through melting point and spectroscopic technique such as 1HNMR only. The synthesized compounds were assessed for acute toxicity test and are proved free of toxicity. The derivatives were further tested as anti-inflammatory agents by in vitro lipoxygenase enzyme inhibition studies, molecular docking, and in vivo carrageenan-induced paw edema assay, and histamine-induced edema test. The overall observations presented that compounds SK1 and SK3 possess promising anti-inflammatory potential, while compound SK2 is found to be a good anti-inflammatory agent.

A Sensitive Electrochemical Aptamer Sensor for Clenbuterol Detection Based on Au NPs/Fe3O4–NH2/GN Nanocomposite

Chronic ingestion of food containing clenbuterol (CLB) in the human body can cause acute poisoning. Thus, it is essential to develop a sensitive CLB detection way. Here, a novel electrochemical aptamer sensor based on aptamer/gold nanoparticles/amino magnetic ferric oxide/graphene nanosheets (aptamer/Au NPs/Fe3O4–NH2/GN) nanocomposite has been developed. The Fe3O4–NH2 nanoparticles were self-assembled on GN, and then Fe3O4–NH2/GN nanocomposite was coated on the glassy carbon electrode (GCE) surface. Afterward, Au NPs were electrodeposited on Fe3O4–NH2/GN nanocomposite to fix the aptamer by the Au–S bonds. When CLB was added to the solution, the aptamer will specifically recognize CLB, causing current changes. Under the optimized conditions, the sensor shows better electrochemical performance (linear range is [Formula: see text][Formula: see text]M to [Formula: see text][Formula: see text]M, the detection limit is [Formula: see text][Formula: see text]M ([Formula: see text])). It has been successfully applied to the detection of CLB in actual samples. The results show that the aptamer sensor has good selectivity, stability and repeatability, which will provide a novel idea for more sensitive and quicker CLB detection.

Investigating Internalization of Reporter-Protein-Functionalized Polyhedrin Particles by Brain Immune Cells.

Achieving sustained drug delivery to the central nervous system (CNS) is a major challenge for neurological injury and disease, and various delivery vehicles are being developed to achieve this. Self-assembling polyhedrin crystals (POlyhedrin Delivery System; PODS) are being exploited for the delivery of therapeutic protein cargo, with demonstrated efficacy in vivo. However, to establish the utility of PODS for neural applications, their handling by neural immune cells (microglia) must be documented, as these cells process and degrade many biomaterials, often preventing therapeutic efficacy. Here, primary mouse cortical microglia were cultured with a GFP-functionalized PODS for 24 h. Cell counts, cell morphology and Iba1 expression were all unaltered in treated cultures, indicating a lack of acute toxicity or microglial activation. Microglia exhibited internalisation of the PODS, with both cytosolic and perinuclear localisation. No evidence of adverse effects on cellular morphology was observed. Overall, 20-40% of microglia exhibited uptake of the PODS, but extracellular/non-internalised PODS were routinely present after 24 h, suggesting that extracellular drug delivery may persist for at least 24 h.

Homologous-targeting biomimetic nanoparticles co-loaded with melittin and a photosensitizer for the combination therapy of triple negative breast cancer.

Melittin (Mel) is considered a promising candidate drug for the treatment of triple negative breast cancer (TNBC) due to its various antitumor effects. However, its clinical application is hampered by notable limitations, including hemolytic activity, rapid clearance, and a lack of tumor selectivity. Here, we designed novel biomimetic nanoparticles based on homologous tumor cell membranes and poly(lactic-co-glycolic acid) (PLGA)/poly(beta-aminoester) (PBAE), denoted MDM@TPP, which efficiently coloaded the cytolytic peptide Mel and the photosensitizer mTHPC. Both in vitro and in vivo, the MDM@TPP nanoparticles effectively mitigated the acute toxicity of melittin and exhibited strong TNBC targeting ability due to the homologous targeting effect of the tumor cell membrane. Under laser irradiation, the MDM@TPP nanoparticles showed excellent photodynamic performance and thus accelerated the release of Mel by disrupting cell membrane integrity. Moreover, Mel combined with photodynamic therapy (PDT) can synergistically kill tumor cells and induce significant immunogenic cell death, thereby stimulating the maturation of dendritic cells (DCs). In 4T1 tumor-bearing mice, MDM@TPP nanoparticles effectively inhibited the growth and metastasis of primary tumors and finally prevented tumor recurrence by improving the immune response.