DNA/RNA-based electrochemical nanobiosensors for early detection of cancers.

Nucleic acids, like DNA and RNA, serve as versatile recognition elements in electrochemical biosensors, demonstrating notable efficacy in detecting various cancer biomarkers with high sensitivity and selectivity. These biosensors offer advantages such as cost-effectiveness, rapid response, ease of operation, and minimal sample preparation. This review provides a comprehensive overview of recent developments in nucleic acid-based electrochemical biosensors for cancer diagnosis, comparing them with antibody-based counterparts. Specific examples targeting key cancer biomarkers, including prostate-specific antigen, microRNA-21, and carcinoembryonic antigen, are highlighted. The discussion delves into challenges and limitations, encompassing stability, reproducibility, interference, and standardization issues. The review suggests future research directions, exploring new nucleic acid recognition elements, innovative transducer materials and designs, novel signal amplification strategies, and integration with microfluidic devices or portable instruments. Evaluating these biosensors in clinical settings using actual samples from cancer patients or healthy donors is emphasized. These sensors are sensitive and specific at detecting non-communicable and communicable disease biomarkers. DNA and RNA's self-assembly, programmability, catalytic activity, and dynamic behavior enable adaptable sensing platforms. They can increase biosensor biocompatibility, stability, signal transduction, and amplification with nanomaterials. In conclusion, nucleic acids-based electrochemical biosensors hold significant potential to enhance cancer detection and treatment through early and accurate diagnosis.

Dendrimers as nanoscale vectors: Unlocking the bars of cancer therapy.

Chemotherapy is the first choice in the treatment of cancer and is always preferred to other approaches such as radiation and surgery, but it has never met the need of patients for a safe and effective drug. Therefore, new advances in cancer treatment are now needed to reduce the side effects and burdens associated with chemotherapy for cancer patients. Targeted treatment using nanotechnology are now being actively explored as they could effectively deliver therapeutic agents to tumor cells without affecting normal cells. Dendrimers are promising nanocarriers with distinct physiochemical properties that have received considerable attention in cancer therapy studies, which is partly due to the numerous functional groups on their surface. In this review, we discuss the progress of different types of dendrimers as delivery systems in cancer therapy, focusing on the challenges, opportunities, and functionalities of the polymeric molecules. The paper also reviews the various role of dendrimers in their entry into cells via endocytosis, as well as the molecular and inflammatory pathways in cancer. In addition, various dendrimers-based drug delivery (e.g., pH-responsive, enzyme-responsive, redox-responsive, thermo-responsive, etc.) and lipid-, amino acid-, polymer- and nanoparticle-based modifications for gene delivery, as well as co-delivery of drugs and genes in cancer therapy with dendrimers, are presented. Finally, biosafety concerns and issues hindering the transition of dendrimers from research to the clinic are discussed to shed light on their clinical applications.

(Nano)platforms in breast cancer therapy: Drug/gene delivery, advanced nanocarriers and immunotherapy.

Breast cancer is the most malignant tumor in women, and there is no absolute cure for it. Although treatment modalities including surgery, chemotherapy, and radiotherapy are utilized for breast cancer, it is still a life-threatening disease for humans. Nanomedicine has provided a new opportunity in breast cancer treatment, which is the focus of the current study. The nanocarriers deliver chemotherapeutic agents and natural products, both of which increase cytotoxicity against breast tumor cells and prevent the development of drug resistance. The efficacy of gene therapy is boosted by nanoparticles and the delivery of CRISPR/Cas9, Noncoding RNAs, and RNAi, promoting their potential for gene expression regulation. The drug and gene codelivery by nanoparticles can exert a synergistic impact on breast tumors and enhance cellular uptake via endocytosis. Nanostructures are able to induce photothermal and photodynamic therapy for breast tumor ablation via cell death induction. The nanoparticles can provide tumor microenvironment remodeling and repolarization of macrophages for antitumor immunity. The stimuli-responsive nanocarriers, including pH-, redox-, and light-sensitive, can mediate targeted suppression of breast tumors. Besides, nanoparticles can provide a diagnosis of breast cancer and detect biomarkers. Various kinds of nanoparticles have been employed for breast cancer therapy, including carbon-, lipid-, polymeric- and metal-based nanostructures, which are different in terms of biocompatibility and delivery efficiency.

Recapitulating Antioxidant and Antibacterial Compounds into a Package for Tissue Regeneration: Dual Function Materials with Synergistic Effect.

Oxidative damage and infection can prevent or delay tissue repair. Moreover, infection reinforces reactive oxygen species (ROS) formation, which makes the wound's condition even worse. Therefore, the need for antioxidant and antibacterial agents is felt for tissue regeneration. There are emerging up-and-coming biomaterials that recapitulate both properties into a package, offering an effective solution to turn the wound back into a healing state. In this article, the principles of antioxidant and antibacterial activity are summarized. The review starts with biological aspects, getting the readers to familiarize themselves with tissue barriers against infection. This is followed by the chemistry and mechanism of action of antioxidant and antibacterial materials (dual function). Eventually, the outlook and challenges are underlined to provide where the dual-function biomaterials are and where they are going in the future. It is expected that the present article inspires the designing of dual-function biomaterials to more advanced levels by providing the fundamentals and comparative points of view and paving the clinical way for these materials.

Stimuli-responsive biomaterials: smart avenue toward 4D bioprinting.

3D bioprinting is an advanced technology combining cells and bioactive molecules within a single bioscaffold; however, this scaffold cannot change, modify or grow in response to a dynamic implemented environment. Lately, a new era of smart polymers and hydrogels has emerged, which can add another dimension, e.g., time to 3D bioprinting, to address some of the current approaches' limitations. This concept is indicated as 4D bioprinting. This approach may assist in fabricating tissue-like structures with a configuration and function that mimic the natural tissue. These scaffolds can change and reform as the tissue are transformed with the potential of specific drug or biomolecules released for various biomedical applications, such as biosensing, wound healing, soft robotics, drug delivery, and tissue engineering, though 4D bioprinting is still in its early stages and more works are required to advance it. In this review article, the critical challenge in the field of 4D bioprinting and transformations from 3D bioprinting to 4D phases is reviewed. Also, the mechanistic aspects from the chemistry and material science point of view are discussed too.

Natural components as surface engineering agents for CRISPR delivery.

This perspective article discusses the potential of using natural and environmentally friendly components as surface engineering agents for CRISPR delivery. Traditional delivery methods for CRISPR have limitations and safety concerns, and surface engineering has emerged as a promising approach. This perspective provides an overview of current research, including the use of lipids, proteins, natural components (like leaf extracts), and polysaccharides to modify the surface of nanoparticles and nanomaterials to improve delivery efficiency, stability, and (in some cases) cellular internalization ability. The advantages of using natural components include biocompatibility, biodegradability, engineered functionality, cost-effectiveness, and environmental friendliness. Also in-depth discusses about the challenges and future perspective of this field, such as a better understanding of underlying mechanisms and optimization of delivery methods for different cell line types and tissues, as well as the generation of novel inorganic nanomaterials, including MOF and MXene, for CRISPR delivery, and their synergistic potentials using leaf extracts and natural components provided. The use of natural components as surface engineering agents for CRISPR delivery has the potential to overcome the limitations of traditional delivery methods, eliminating the biological and physicochemical challenges, and represents a promising area of research.

Natural resources for sustainable synthesis of nanomaterials with anticancer applications: A move toward green nanomedicine.

Today, researchers have focused on the application of environmentally-benign and sustainable micro- and nanosystems for drug delivery and cancer therapy. Compared to conventional chemotherapeutics, advanced micro- and nanosystems designed by applying abundant, natural, and renewable feedstocks have shown biodegradability, biocompatibility, and low toxicity advantages. However, important aspects of toxicological assessments, clinical translational studies, and suitable functionalization/modification still need to be addressed. Herein, the benefits and challenges of green nanomedicine in cancer nanotherapy and targeted drug delivery are cogitated using nanomaterials designed by exploiting natural and renewable resources. The application of nanomaterials accessed from renewable natural resources, comprising metallic nanomaterials, carbon-based nanomaterials, metal-organic frameworks, natural-derived nanomaterials, etc. for targeted anticancer drug delivery and cancer nanotherapy are deliberated, with emphasis on important limitations/challenges and future perspectives.

Co-delivery of doxorubicin/sorafenib by DNA-decorated green ZIF-67-based nanocarriers for chemotherapy and hepatocellular carcinoma treatment.

Zeolitic imidazolate framework-67 (ZIF-67) has been decorated with natural biomaterials and DNA to develop a promising strategy and suitable and safe co-delivery platform for doxorubicin and sorafenib (DOX-SOR). FT-IR, XRD, FESEM, and TEM were used to characterize the modified MOFs. Combined Ginkgo biloba leaf extract and E. coli DNA were used as green decorations, and as environmentally-friendly methods to be developed, and DOX and SOR were attached to the porosity and on the surface of the MOFs. TEM and FESEM images demonstrated that the green MOFs were successfully synthesized for biomedical applications and showed their cubic structure. As a result of the nanocarrier-drug interactions, 59.7% and 60.2% of the drug payload were achieved with DOX and SOR, respectively. HEK-293, HT-29, and MCF-7 cells displayed excellent viability by decoration with DNA and Ginkgo biloba leaf extract at low and high concentrations (0.1 and 50 µg/mL), suggesting they could be used in biomedical applications. MTT assays demonstrated that the nanocarriers are highly biocompatible with normal cells and possess anticancer properties when applied to HT-29 and MCF-7 cells. As a result of Ginkgo biloba leaf extract and DNA modification, DOX-SOR release was prolonged and pH-sensitive (highest release at pHs 4.5 and 5.5). The internalization and delivery of the drug were also studied using a 2d fluorescence microscope, demonstrating that the drug was effectively internalized. Cell images showed NPs internalizing in MCF-7 cells, proving their efficacy as drug delivery systems.

Green and Sustainable Membranes: A review.

Membranes are ubiquitous tools for modern water treatment technology that critically eliminate hazardous materials such as organic, inorganic, heavy metals, and biomedical pollutants. Nowadays, nano-membranes are of particular interest for myriad applications such as water treatment, desalination, ion exchange, ion concentration control, and several kinds of biomedical applications. However, this state-of-the-art technology suffers from some drawbacks, e.g., toxicity and fouling of contaminants, which makes the synthesis of green and sustainable membranes indeed safety-threatening. Typically, sustainability, non-toxicity, performance optimization, and commercialization are concerns centered on manufacturing green synthesized membranes. Thus, critical issues related to toxicity, biosafety, and mechanistic aspects of green-synthesized nano-membranes have to be systematically and comprehensively reviewed and discussed. Herein we evaluate various aspects of green nano-membranes in terms of their synthesis, characterization, recycling, and commercialization aspects. Nanomaterials intended for nano-membrane development are classified in view of their chemistry/synthesis, advantages, and limitations. Indeed, attaining prominent adsorption capacity and selectivity in green-synthesized nano-membranes requires multi-objective optimization of a number of materials and manufacturing parameters. In addition, the efficacy and removal performance of green nano-membranes are analyzed theoretically and experimentally to provide researchers and manufacturers with a comprehensive image of green nano-membrane efficiency under real environmental conditions.

Nanostructures for prevention, diagnosis, and treatment of viral respiratory infections: from influenza virus to SARS-CoV-2 variants.

Viruses are a major cause of mortality and socio-economic downfall despite the plethora of biopharmaceuticals designed for their eradication. Conventional antiviral therapies are often ineffective. Live-attenuated vaccines can pose a safety risk due to the possibility of pathogen reversion, whereas inactivated viral vaccines and subunit vaccines do not generate robust and sustained immune responses. Recent studies have demonstrated the potential of strategies that combine nanotechnology concepts with the diagnosis, prevention, and treatment of viral infectious diseases. The present review provides a comprehensive introduction to the different strains of viruses involved in respiratory diseases and presents an overview of recent advances in the diagnosis and treatment of viral infections based on nanotechnology concepts and applications. Discussions in diagnostic/therapeutic nanotechnology-based approaches will be focused on H1N1 influenza, respiratory syncytial virus, human parainfluenza virus type 3 infections, as well as COVID-19 infections caused by the SARS-CoV-2 virus Delta variant and new emerging Omicron variant.

Clickable Polysaccharides for Biomedical Applications: A Comprehensive Review.

Recent advances in materials science and engineering highlight the importance of designing sophisticated biomaterials with well-defined architectures and tunable properties for emerging biomedical applications. Click chemistry, a powerful method allowing specific and controllable bioorthogonal reactions, has revolutionized our ability to make complex molecular structures with a high level of specificity, selectivity, and yield under mild conditions. These features combined with minimal byproduct formation have enabled the design of a wide range of macromolecular architectures from quick and versatile click reactions. Furthermore, copper-free click chemistry has resulted in a change of paradigm, allowing researchers to perform highly selective chemical reactions in biological environments to further understand the structure and function of cells. In living systems, introducing clickable groups into biomolecules such as polysaccharides (PSA) has been explored as a general approach to conduct medicinal chemistry and potentially help solve healthcare needs. De novo biosynthetic pathways for chemical synthesis have also been exploited and optimized to perform PSA-based bioconjugation inside living cells without interfering with their native processes or functions. This strategy obviates the need for laborious and costly chemical reactions which normally require extensive and time-consuming purification steps. Using these approaches, various PSA-based macromolecules have been manufactured as building blocks for the design of novel biomaterials. Clickable PSA provides a powerful and versatile toolbox for biomaterials scientists and will increasingly play a crucial role in the biomedical field. Specifically, bioclick reactions with PSA have been leveraged for the design of advanced drug delivery systems and minimally invasive injectable hydrogels. In this review article, we have outlined the key aspects and breadth of PSA-derived bioclick reactions as a powerful and versatile toolbox to design advanced polymeric biomaterials for biomedical applications such as molecular imaging, drug delivery, and tissue engineering. Additionally, we have also discussed the past achievements, present developments, and recent trends of clickable PSA-based biomaterials such as 3D printing, as well as their challenges, clinical translatability, and future perspectives.

Viral and non-viral gene therapy using 3D (bio)printing.

The overall success in launching discovered drugs is tightly restricted to the high rate of late-stage failures, which ultimately inhibits the distribution of medicines in markets. As a result, it is imperative that methods reliably predict the effectiveness and, more critically, the toxicity of medicine early in the drug development process before clinical trials be continuously innovated. We must stay up to date with the fast appearance of new infections and diseases by rapidly developing the requisite vaccinations and medicines. Modern in vitro models of disease may be used as an alternative to traditional disease models, and advanced technology can be used for the creation of pharmaceuticals as well as cells, drugs, and gene delivery systems to expedite the drug discovery procedure. Furthermore, in vitro models that mimic the spatial and chemical characteristics of native tissues, such as a 3D bioprinting system or other technologies, have proven to be more effective for drug screening than traditional 2D models. Viral and non-viral gene delivery vectors are a hopeful tool for combinatorial gene therapy, suggesting a quick way of simultaneously deliver multiple genes. A 3D bioprinting system embraces an excellent potential for gene delivery into the different cells or tissues for different diseases, in tissue engineering and regeneration medicine, in which the precise nucleic acid is located in the 3D printed tissues and scaffolds. Non-viral nanocarriers, in combination with 3D printed scaffolds, are applied to their delivery of genes and controlled release properties. There remains, however, a big obstacle in reaching the full potential of 3D models because of a lack of in vitro manufacturing of live tissues. Bioprinting advancements have made it possible to create biomimetic constructions that may be used in various drug discovery research applications. 3D bioprinting also benefits vaccinations, medicines, and relevant delivery methods because of its flexibility and adaptability. This review discusses the potential of 3D bioprinting technologies for pharmaceutical studies.

Histidine-enhanced gene delivery systems: The state of the art.

Gene therapy has emerged as a promising tool for treating different intractable diseases, particularly cancer or even viral diseases such as COVID-19 (coronavirus disease 2019). In this context, various non-viral gene carriers are being explored to transfer DNA or RNA sequences into target cells. Here, we review the applications of the naturally occurring amino acid histidine in the delivery of nucleic acids into cells. The biocompatibility of histidine-enhanced gene delivery systems has encouraged their wider use in gene therapy. Histidine-based gene carriers can involve the modification of peptides, dendrimers, lipids or nanocomposites. Several linear polymers, such as polyethylenimine, poly-l-lysine (synthetic) or dextran and chitosan (natural), have been conjugated with histidine residues to form complexes with nucleic acids for intracellular delivery. The challenges, opportunities and future research trends of histidine-based gene deliveries are investigated.

The colorful world of carotenoids: a profound insight on therapeutics and recent trends in nano delivery systems.

The therapeutic effects of carotenoids as dietary supplements to control or even treat some specific diseases including diabetic retinopathy, cardiovascular diseases, bacterial infections, as well as breast, prostate, and skin cancer are discussed in this review and also thoughts on future research for their widespread use are emphasized. From the stability standpoint, carotenoids have low bioavailability and bioaccessibility owing to their poor water solubility, deterioration in the presence of environmental stresses such as oxygen, light, and high heat as well as rapid degradation during digestion. Nanoencapsulation technologies as wall or encapsulation materials have been increasingly used for improving food product functionality. Nanoencapsulation is a versatile process employed for the protection, entrapment, and the delivery of food bioactive products including carotenoids from diverse environmental conditions for extended shelf lives and for providing controlled release. Therefore, we present here, recent (mostly during the last five years) nanoencapsulation methods of carotenoids with various nanocarriers. To us, this review can be considered as the first highlighting not only the potential therapeutic effects of carotenoids on various diseases but also their most effective nanodelivery systems.HighlightsBioactive compounds are of deep interest to improve food properties.Carotenoids (such as ß-carotene and xanthophylls) play indispensable roles in maintaining human health and well-being.A substantial research effort has been carried out on developing beneficial nanodelivery systems for various carotenoids.Nanoencapsulation of carotenoids can enhance their functional properties.Stable nanoencapsulated carotenoids could be utilized in food products.

Potential nanotechnology-based diagnostic and therapeutic approaches for Meniere's disease.

Meniere's disease (MD) is a progressive inner ear disorder involving recurrent and prolonged episodes or attacks of vertigo with associated symptoms, resulting in a significantly reduced quality of life for sufferers. In most cases, MD starts in one ear; however, in one-third of patients, the disorder progresses to the other ear. Unfortunately, the etiology of the disease is unknown, making the development of effective treatments difficult. Nanomaterials, including nanoparticles (NPs) and nanocarriers, offer an array of novel diagnostic and therapeutic applications related to MD. NPs have specific features such as biocompatibility, biochemical stability, targetability, and enhanced visualization using imaging tools. This paper provides a comprehensive and critical review of recent advancements in nanotechnology-based diagnostic and therapeutic approaches for MD. Furthermore, the crucial challenges adversely affecting the use of nanoparticles to treat middle ear disorders are investigated. Finally, this paper provides recommendations and future directions for improving the performances of nanomaterials on theragnostic applications of MD.

Quantum dots against SARS-CoV-2: diagnostic and therapeutic potentials.

The application of quantum dots (QDs) for detecting and treating various types of coronaviruses is very promising, as their low toxicity and high surface performance make them superior among other nanomaterials; in conjugation with fluorescent probes they are promising semiconductor nanomaterials for the detection of various cellular processes and viral infections. In view of the successful results for inhibiting SARS-CoV-2, functional QDs could serve eminent role in the growth of safe nanotherapy for the cure of viral infections in the near future; their large surface areas help bind numerous molecules post-synthetically. Functionalized QDs with high functionality, targeted selectivity, stability and less cytotoxicity can be employed for highly sensitive co-delivery and imaging/diagnosis. Besides, due to the importance of safety and toxicity issues, QDs prepared from plant sources (e.g. curcumin) are much more attractive, as they provide good biocompatibility and low toxicity. In this review, the recent developments pertaining to the diagnostic and inhibitory potentials of QDs against SARS-CoV-2 are deliberated including important challenges and future outlooks. © 2022 Society of Chemical Industry (SCI).

Biowaste-Derived Carbon Dots: A Perspective on Biomedical Potentials.

Today, sustainable and natural resources including biowastes have been considered attractive starting materials for the fabrication of biocompatible and biodegradable carbon dots (CDs) due to the benefits of availability, low cost, biorenewability, and environmentally benign attributes. These carbonaceous nanomaterials have been widely explored in the field of sensing/imaging, optoelectronics, photocatalysis, drug/gene delivery, tissue engineering, regenerative medicine, and cancer theranostics. Designing multifunctional biowaste-derived CDs with a high efficacy-to-toxicity ratio for sustained and targeted drug delivery, along with imaging potentials, opens a new window of opportunity toward theranostic applications. However, crucial challenges regarding the absorption/emission wavelength, up-conversion emission/multiphoton fluorescence mechanisms, and phosphorescence of these CDs still need to be addressed to attain the maximum functionality and efficacy. Future studies ought to focus on optimizing the synthesis techniques/conditions, evaluating the influence of nucleation/growth process on structures/properties, controlling their morphology/size, and finding the photoluminescence mechanisms. Reproducibility of synthesis techniques is another critically important factor that needs to be addressed in the future. Herein, the recent developments related to the biowaste-derived CDs with respect to their biomedical applications are deliberated, focusing on important challenges and future perspectives.

Use of Biochar Prepared from the Açaí Seed as Adsorbent for the Uptake of Catechol from Synthetic Effluents.

This work proposes a facile methodology for producing porous biochar material (ABC) from açaí kernel residue, produced by chemical impregnation with ZnCl2 (1:1) and pyrolysis at 650.0 °C. The characterization was achieved using several techniques, and the biochar material was employed as an adsorbent to remove catechol. The results show that ABC carbon has hydrophilic properties. The specific surface area and total pore volume are 1315 m2·g−1 and 0.7038 cm3·g−1, respectively. FTIR revealed the presence of oxygenated groups, which can influence catechol adsorption. The TGA/DTG indicated that the sample is thermally stable even at 580 °C. Adsorption studies showed that equilibrium was achieved in <50 min and the Avrami kinetic model best fits the experimental data, while Freundlich was observed to be the best-fitted isotherm model. Catechol adsorption on ABC biochar is governed by van der Waals forces and microporous and mesoporous filling mechanisms. The Qmax is 339.5 mg·g−1 (40 °C) with 98.36% removal of simulated effluent, showing that açaí kernel is excellent biomass to prepare good biochar that can be efficiently used to treat real industrial effluents.

Improved green biosynthesis of chitosan decorated Ag- and Co3O4-nanoparticles: A relationship between surface morphology, photocatalytic and biomedical applications.

AgNPs@Chitosan and Co3O4-NPs@Chitosan were fabricated with Salvia hispanica. Results showed MZI values of 5 and 30 mm for Co3O4-NPs- and AgNPs@Chitosan against S. aureus, and 15 and 21 mm for Co3O4-NPs- and AgNPs@Chitosan against E. coli (24 h, 20 µg/mL), respectively. MTT assays showed up to 80% and 90%, 71% and 75%, and 91% and 94% mammalian cell viability for the green synthesized, chemically synthesized AgNPs and green synthesized AgNPs@Chitosan for HEK-293 and PC12 cells, respectively, and 70% and 71%, 59% and 62%, and 88% and 73% for the related Co3O4-NPs (24 h, 20 µg/mL). The photocatalytic activities showed dye degradation after 135 and 105 min for AgNPs@Chitosan and Co3O4-NPs@Chitosan, respectively. FESEM results showed differences in particle sizes (32 ±â€¯3.0 nm for the AgNPs and 41 ±â€¯3.0 nm for the Co3O4NPs) but AFM results showed lower roughness of the AgNPs@Chitosan (7.639 ±â€¯0.85 nm) compared to Co3O4NPs@Chitosan (9.218 ±â€¯0.93 nm), which resulted in potential biomedical applications.

Electrocardiographic Changes in Children With Acute Opioid Poisoning: A Cross-Sectional Study.

OBJECTIVES: Opioid poisoning in children is a common pediatric emergency in Iran. The emergence and spread of new synthetic opioids have come up with new consequences in case of toxicity. In this study, we aimed to evaluate electrocardiographic changes in children with acute opiate poisoning. METHODS: This cross-sectional study was performed on all children with opioid poisoning admitted to the emergency ward of Vali-e-Asr Hospital, Birjand, Iran, from December 2015 to February 2017. Data (demographics, manifestations, clinical course, and outcome) were collected using a predesigned checklist. An electrocardiogram (ECG) was obtained and evaluated for arrhythmias, corrected QT interval (QTc), and other ECG indices. Data were analyzed using SPSS version 21. A value of P less than 0.05 was considered statistically significant. RESULTS: A total of 85 children were enrolled in this study. Most of them were male (51.8%). The mean age of the patients was 3.46 ± 3.36 years. Among these children, 38.8% were poisoned with synthetic opioids (methadone). Mean QTc length was 399 ± 24 milliseconds in nonsynthetic opioid poisoning and 407 ± 66 milliseconds in methadone poisoning, and it was prolonged (>450 milliseconds) in 3.5% of cases. Other ECG changes were limited to 1 U wave formation (1.2%) that was detected in a patient with methadone poisoning. CONCLUSIONS: Electrocardiogram changes due to acute opioid toxicity in children are not common, although in the case of methadone poisoning, long QT interval and associated arrhythmias should be anticipated. Moreover, because of life-threatening effects of opioids such as respiratory insufficiency and decreased consciousness, it is necessary to be prepared for these conditions.