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1
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Janicka M, Chodkowski M, Osinska A, Bylinska K, Obuch-Woszczatyńska O, Patrycy M, Chodaczek G, Ranoszek-Soliwoda K, Tomaszewska E, Celichowski G, Grobelny J, Cymerys J, Krzyżowska M. Adjuvanticity of Tannic Acid-Modified Nanoparticles Improves Effectiveness of the Antiviral Response. Int J Nanomedicine 2025; 20:3977-3997. [PMID: 40191045 PMCID: PMC11972000 DOI: 10.2147/ijn.s512509] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2025] [Accepted: 03/13/2025] [Indexed: 04/09/2025] Open
Abstract
Introduction Herpes simplex virus type 1 (HSV-1) causes recurrent infections of skin and mucosal tissues with high global prevalence. HSV-1 also invades the nervous system where it establishes a lifelong latency-making infection poorly treatable We previously showed that both tannic acid-modified silver and gold nanoparticles (TA-Ag/AuNPs) inhibit HSV-1 infection in vitro. Methods We used an in vitro and in vivo model of HSV-1 infection to study how metal type, size and tannic acid modification of nanoparticles can influence development of the early innate response and the mounting of specific anti-HSV-1 response upon treatment of the nasal mucosa. Results We found that tannic acid is necessary for binding with HSV-1, with smaller sizes independent of the NPs composition, whereas for larger NPs, only TA-AgNPs can inhibit HSV-1 infection. Intranasal treatment of HSV-1 infection with TA-Ag/AuNPs results in lower viral titers and a better antiviral response, followed by increased IFN-α, CXCL9, and CXCL10 levels as well as infiltration of T cells and NK cells in the infected sites. We also found that the application of TA-NPs to the nasal cavities of infected mice induced infiltration of both monocytes and Langerhans cells (LCs), which lasted longer compared to the application of unmodified NPs. Furthermore, TA-NPs activated monocytes and microglia to produce antiviral cytokines and chemokines better than unmodified NPs, except for the large TA-AuNPs. Discussion Treatment of the mucosal tissues at the early stage of HSV-1 infection helps to modulate specific and effective antiviral immune response by attracting cytotoxic lymphocytes and inducing the production of antiviral cytokines and chemokines. Furthermore, tannic acid modification is helpful for the removal of nanoparticles from the respiratory tract, which increases the safety of nanoparticle applications to treat infections.
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Affiliation(s)
- Martyna Janicka
- Division of Medical and Environmental Microbiology, Military Institute of Hygiene and Epidemiology, Warsaw, Poland
- Division of Microbiology, Department of Preclinical Sciences, Institute of Veterinary Medicine, Warsaw University of Life Sciences, Warsaw, Poland
| | - Marcin Chodkowski
- Division of Medical and Environmental Microbiology, Military Institute of Hygiene and Epidemiology, Warsaw, Poland
| | - Aleksandra Osinska
- Division of Medical and Environmental Microbiology, Military Institute of Hygiene and Epidemiology, Warsaw, Poland
| | - Klaudia Bylinska
- Laboratory of Parasitology, Military Institute of Hygiene and Epidemiology, Warsaw, Poland
- Division of Pharmacology and Toxicology, Department of Preclinical Sciences, Institute of Veterinary Medicine, Warsaw University of Life Sciences, Warsaw, Poland
| | - Oliwia Obuch-Woszczatyńska
- Laboratory of Parasitology, Military Institute of Hygiene and Epidemiology, Warsaw, Poland
- Division of Pharmacology and Toxicology, Department of Preclinical Sciences, Institute of Veterinary Medicine, Warsaw University of Life Sciences, Warsaw, Poland
| | - Magdalena Patrycy
- Division of Medical and Environmental Microbiology, Military Institute of Hygiene and Epidemiology, Warsaw, Poland
| | - Grzegorz Chodaczek
- Łukasiewicz Research Network – PORT Polish Center for Technology Development, Life Sciences and Biotechnology Center, Wroclaw, Poland
| | | | - Emilia Tomaszewska
- University of Lodz, Faculty of Chemistry, Department of Materials Technology and Chemistry, Lodz, Poland
| | - Grzegorz Celichowski
- University of Lodz, Faculty of Chemistry, Department of Materials Technology and Chemistry, Lodz, Poland
| | - Jaroslaw Grobelny
- University of Lodz, Faculty of Chemistry, Department of Materials Technology and Chemistry, Lodz, Poland
| | - Joanna Cymerys
- Division of Microbiology, Department of Preclinical Sciences, Institute of Veterinary Medicine, Warsaw University of Life Sciences, Warsaw, Poland
| | - Małgorzata Krzyżowska
- Division of Medical and Environmental Microbiology, Military Institute of Hygiene and Epidemiology, Warsaw, Poland
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Rentschler KM, Kodavanti UP. Mechanistic insights regarding neuropsychiatric and neuropathologic impacts of air pollution. Crit Rev Toxicol 2024; 54:953-980. [PMID: 39655487 PMCID: PMC12043015 DOI: 10.1080/10408444.2024.2420972] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2024] [Revised: 10/07/2024] [Accepted: 10/15/2024] [Indexed: 12/24/2024]
Abstract
Air pollution is a significant environmental health risk for urban areas and developing countries. Air pollution may contribute to the incidence of cardiopulmonary and metabolic diseases. Evidence also points to the role of air pollution in worsening or developing neurological and neuropsychiatric conditions. Inhaled pollutants include compositionally differing mixtures of respirable gaseous and particulate components of varied sizes, solubilities, and chemistry. Inhalation of combustibles and volatile organic compounds (VOCs) or other irritant particulate matter (PM) may trigger lung sensory afferents which initiate a sympathetic stress response via activation of the hypothalamic-pituitary-adrenal (HPA) and sympathetic-adrenal-medullary (SAM) axes. Activation of SAM and HPA axes are associated with selective inhibition of hypothalamic-pituitary-gonadal (HPG) and hypothalamic-pituitary-thyroid (HPT) axes following exposure. Regarding chronic exposure in susceptible hosts, these changes may become pathological by causing neuroinflammation, neurotransmitter, and neuroendocrine imbalances. Soluble PM, such as metals and nano-size particles may translocate across the olfactory, trigeminal, or vagal nerves through retrograde axonal transport, or through systemic circulation which may disrupt the blood-brain barrier (BBB) and deposit in neural tissue. Neuronal deposition of metallic components can have a negative impact through multiple molecular mechanisms. In addition to systemic translocation, the release of pituitary and stress hormones, altered metabolic hormonal status and resultant circulating metabolic milieu, and sympathetically and HPA-mediated changes in immune markers, may secondarily impact the brain through a variety of regulatory adrenal hormone-dependent mechanisms. Several reviews covering air pollution as a risk factor for neuropsychiatric disorders have been published, but no reviews discuss the in-depth intersection between molecular and stress-related neuroendocrine mechanisms, thereby addressing adaptation and susceptibility variations and link to peripheral tissue effects. The purpose of this review is to discuss evidence regarding neurochemical, neuroendocrine, and molecular mechanisms which may contribute to neuropathology from air pollution exposure. This review also covers bi-directional neural and systemic interactions which may raise the risk for air pollution-related systemic illness.
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Affiliation(s)
- Katherine M. Rentschler
- Oak Ridge Institute for Science and Education Research Participation Program, U.S. Environmental Protection Agency, Research Triangle Park, NC, United States of America
| | - Urmila P. Kodavanti
- Public Health and Integrated Toxicology Division, Center for Public Health and Environmental Assessment, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina, United States of America
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Maaz A, Blagbrough IS, De Bank PA. Gold Nanoparticles: Tunable Characteristics and Potential for Nasal Drug Delivery. Pharmaceutics 2024; 16:669. [PMID: 38794331 PMCID: PMC11125093 DOI: 10.3390/pharmaceutics16050669] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2024] [Revised: 04/10/2024] [Accepted: 05/09/2024] [Indexed: 05/26/2024] Open
Abstract
A general procedure to prepare gold nanourchins (GNUs) via a seed-mediated method was followed using dopamine hydrochloride as a reducing agent and silver nitrate salt (AgNO3) as a shape-directing agent. The novelty of this study comes from the successful incorporation of the prepared gold urchins as an aqueous suspension in a nasal pressurized metered dose inhaler (pMDI) formulation and the investigation of their potential for olfactory targeting for direct nose-to-brain drug delivery (NTBDD). The developed pMDI formulation was composed of 0.025% w/w GNUs, 2% w/w Milli-Q water, and 2% w/w EtOH, with the balance of the formulation being HFA134a propellant. Particle integrity and aerosolization performance were examined using an aerosol exposure system, whereas the nasal deposition profile was tested in a sectioned anatomical replica of human nasal airways. The compatibility of the gold dispersion with the nasal epithelial cell line RPMI 2650 was also investigated in this study. Colloidal gold was found to be stable following six-month storage at 4 °C and during the lyophilization process utilizing a pectin matrix for complete re-dispersibility in water. The GNUs were intact and discrete following atomization via a pMDI, and 13% of the delivered particles were detected beyond the nasal valve, the narrowest region in the nasal cavity, out of which 5.6% was recovered from the olfactory region. Moreover, the formulation was found to be compatible with the human nasal epithelium cell line RPMI 2650 and excellent cell viability was observed. The formulated GNU-HFA-based pMDI is a promising approach for intranasal drug delivery, including deposition in the olfactory region, which could be employed for NTBDD applications.
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Affiliation(s)
- Aida Maaz
- Department of Life Sciences, University of Bath, Bath BA2 7AY, UK
| | | | - Paul A. De Bank
- Department of Life Sciences, University of Bath, Bath BA2 7AY, UK
- Centre for Therapeutic Innovation, University of Bath, Bath BA2 7AY, UK
- Centre for Bioengineering & Biomedical Technologies, University of Bath, Bath BA2 7AY, UK
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4
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Khan J, Yadav S. Nanotechnology-based Nose-to-brain Delivery in Epilepsy: A NovelApproach to Diagnosis and Treatment. Pharm Nanotechnol 2024; 12:314-328. [PMID: 37818558 DOI: 10.2174/0122117385265554230919070402] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2023] [Revised: 08/09/2023] [Accepted: 08/13/2023] [Indexed: 10/12/2023]
Abstract
Epilepsy is a serious neurological disease, and scientists have a significant challenge in developing a noninvasive treatment for the treatment of epilepsy. The goal is to provide novel ideas for improving existing and future anti-epileptic medications. The injection of nano treatment via the nose to the brain is being considered as a possible seizure control method. Various nasal medicine nanoformulations have the potential to cure epilepsy. Investigations with a variety of nose-to-brain dosing methods for epilepsy treatment have yielded promising results. After examining global literature on nanotechnology and studies, the authors propose nasal administration with nanoformulations as a means to successfully treat epilepsy. The goal of this review is to look at the innovative application of nanomedicine for epilepsy treatment via nose-to-brain transfer, with a focus on the use of nanoparticles for load medicines. When nanotechnology is combined with the nose to brain approach, treatment efficacy can be improved through site specific delivery. Furthermore, this technique of administration decreases adverse effects and patient noncompliance encountered with more traditional procedures.
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Affiliation(s)
- Javed Khan
- Department of Pharmacy, School of Medical and Allied Sciences, Galgotias University, Greater Noida, Uttar Pradesh, India
| | - Shikha Yadav
- Department of Pharmacy, School of Medical and Allied Sciences, Galgotias University, Greater Noida, Uttar Pradesh, India
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Lee JH, Chapman DV, Saltzman WM. Nanoparticle Targeting with Antibodies in the Central Nervous System. BME FRONTIERS 2023; 4:0012. [PMID: 37849659 PMCID: PMC10085254 DOI: 10.34133/bmef.0012] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2022] [Accepted: 02/19/2023] [Indexed: 10/19/2023] Open
Abstract
Treatments for disease in the central nervous system (CNS) are limited because of difficulties in agent penetration through the blood-brain barrier, achieving optimal dosing, and mitigating off-target effects. The prospect of precision medicine in CNS treatment suggests an opportunity for therapeutic nanotechnology, which offers tunability and adaptability to address specific diseases as well as targetability when combined with antibodies (Abs). Here, we review the strategies to attach Abs to nanoparticles (NPs), including conventional approaches of chemisorption and physisorption as well as attempts to combine irreversible Ab immobilization with controlled orientation. We also summarize trends that have been observed through studies of systemically delivered Ab-NP conjugates in animals. Finally, we discuss the future outlook for Ab-NPs to deliver therapeutics into the CNS.
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Affiliation(s)
| | | | - W. Mark Saltzman
- Department of Biomedical Engineering, Yale University, New Haven, CT, USA
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Pathak D, Sriram K. Molecular Mechanisms Underlying Neuroinflammation Elicited by Occupational Injuries and Toxicants. Int J Mol Sci 2023; 24:2272. [PMID: 36768596 PMCID: PMC9917383 DOI: 10.3390/ijms24032272] [Citation(s) in RCA: 25] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2022] [Revised: 01/17/2023] [Accepted: 01/17/2023] [Indexed: 01/26/2023] Open
Abstract
Occupational injuries and toxicant exposures lead to the development of neuroinflammation by activating distinct mechanistic signaling cascades that ultimately culminate in the disruption of neuronal function leading to neurological and neurodegenerative disorders. The entry of toxicants into the brain causes the subsequent activation of glial cells, a response known as 'reactive gliosis'. Reactive glial cells secrete a wide variety of signaling molecules in response to neuronal perturbations and thus play a crucial role in the progression and regulation of central nervous system (CNS) injury. In parallel, the roles of protein phosphorylation and cell signaling in eliciting neuroinflammation are evolving. However, there is limited understanding of the molecular underpinnings associated with toxicant- or occupational injury-mediated neuroinflammation, gliosis, and neurological outcomes. The activation of signaling molecules has biological significance, including the promotion or inhibition of disease mechanisms. Nevertheless, the regulatory mechanisms of synergism or antagonism among intracellular signaling pathways remain elusive. This review highlights the research focusing on the direct interaction between the immune system and the toxicant- or occupational injury-induced gliosis. Specifically, the role of occupational injuries, e.g., trips, slips, and falls resulting in traumatic brain injury, and occupational toxicants, e.g., volatile organic compounds, metals, and nanoparticles/nanomaterials in the development of neuroinflammation and neurological or neurodegenerative diseases are highlighted. Further, this review recapitulates the recent advancement related to the characterization of the molecular mechanisms comprising protein phosphorylation and cell signaling, culminating in neuroinflammation.
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Affiliation(s)
| | - Krishnan Sriram
- Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV 26505, USA
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Suthar JK, Vaidya A, Ravindran S. Toxic implications of silver nanoparticles on the central nervous system: A systematic literature review. J Appl Toxicol 2023; 43:4-21. [PMID: 35285037 DOI: 10.1002/jat.4317] [Citation(s) in RCA: 21] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2022] [Revised: 03/07/2022] [Accepted: 03/07/2022] [Indexed: 12/16/2022]
Abstract
Silver nanoparticles have many medical and commercial applications, but their effects on human health are poorly understood. They are used extensively in products of daily use, but little is known about their potential neurotoxic effects. A xenobiotic metal, silver, has no known physiological significance in the human body as a trace metal. Biokinetics of silver nanoparticles indicates its elimination from the body via urine and feces route. However, a substantial amount of evidence from both in vitro and in vivo experimental research unequivocally establish the fact of easier penetration of smaller nanoparticles across the blood-brain barrier to enter in brain and thereby interaction with cellular components to induce neurotoxic effects. Toxicological effects of silver nanoparticles rely on the degree of exposure, particle size, surface coating, and agglomeration state as well as the type of cell or organism used to evaluate its toxicity. This review covers pertinent facts and the present state of knowledge about the neurotoxicity of silver nanoparticles reviewing the impacts on oxidative stress, neuroinflammation, mitochondrial function, neurodegeneration, apoptosis, and necrosis. The effect of silver nanoparticles on the central nervous system is a topic of growing interest and concern that requires immediate consideration.
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Affiliation(s)
- Jitendra Kumar Suthar
- Symbiosis School of Biological Sciences, Faculty of Health Sciences, Symbiosis International (Deemed) University, Pune, India
| | - Anuradha Vaidya
- Symbiosis School of Biological Sciences, Faculty of Health Sciences, Symbiosis International (Deemed) University, Pune, India.,Symbiosis Centre for Stem Cell Research, Symbiosis International (Deemed) University, Pune, India
| | - Selvan Ravindran
- Symbiosis School of Biological Sciences, Faculty of Health Sciences, Symbiosis International (Deemed) University, Pune, India
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Zhang J, Yang Y, Al-Ahmady ZS, Du W, Duan J, Liao Z, Sun Q, Wei Z, Hua J. Maternal exposure to PM 2.5 induces cognitive impairment in offspring via cerebellar neuroinflammation and oxidative stress. ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY 2023; 249:114425. [PMID: 38321695 DOI: 10.1016/j.ecoenv.2022.114425] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/14/2022] [Revised: 12/09/2022] [Accepted: 12/10/2022] [Indexed: 09/02/2023]
Abstract
Available evidence suggest that exposure to PM2.5 during pregnancy is associated with reduced cognitive function in offspring. This study aimed to investigate the effects of maternal exposure to PM2.5 on offspring cognitive function and to elucidate the underlying mechanisms. In this work, pregnant C57BL/6 female mice were exposed to concentrated ambient PM2.5 or filtered air from day 0.5 (=vaginal plug) to day 15.5 in the Shanghai Meteorological and Environmental Animal Exposure System, and offspring cerebellar tissues were collected on embryonic day 15.5, as well as postnatal days 0, 10 and 42. The mean PM2.5 concentrations exposed to the pregnant mice were 73.06 ± 4.90 μg/m3 and 11.15 ± 2.71 μg/m3 in the concentrated ambient PM2.5 and filtered air chambers, respectively. Maternal concentrated PM2.5 exposure was negatively correlated with offspring spatial memory significantly as assessed by the Morris water maze. Compared with the filtered air group, PM2.5-exposed offspring mice had reduced cerebellar microglia. Both RNA and protein levels of IL-8 and TNF-α were elevated in the concentrated ambient PM2.5 group. PM2.5 exposure increased the level of 8-OHG in miRNA of microglia and Purkinje cells in 6-week-old offspring. The level of prostaglandin F2α (8-iso-PGF2Aα) in the cerebellum was increased at different growing stages of offspring after gestational exposure of PM2.5. These results suggested that maternal air pollution exposure might cause inflammatory damage and oxidative stress to the cerebellum, contributing to reduced cognitive performance in mice offspring.
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Affiliation(s)
- Jiajia Zhang
- Shanghai Key Laboratory of Maternal Fetal Medicine, Department of Women and Children's Health Care, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai 200092, China
| | - Yingying Yang
- Clinical Research Center, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai 200092, China
| | - Zahraa S Al-Ahmady
- Pharmacology Department, School of Science and Technology, Nottingham Trent University, Nottingham NG11 8NS, United Kingdom; Division of Pharmacy and Optometry, Faculty of Biology, Medicine and Health, AV Hill Building, The University of Manchester, Manchester M13 9PT, United Kingdom
| | - Wenchong Du
- NTU Psychology, School of Social Sciences, Nottingham Trent University, Nottingham NG1 1BU, United Kingdom
| | - Jinjin Duan
- Drug Discovery and Design Center, the Center for Chemical Biology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medical, Chinese Academy of Sciences, Shanghai 201203, China
| | - Zehuan Liao
- School of Biological Sciences, Nanyang Technological University, Singapore, Singapore; Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Biomedicum, Solnavägen 9, SE-17177 Stockholm, Sweden
| | - Qinghua Sun
- School of Public Health, Zhejiang Chinese Medical University, Zhejiang 310053, China
| | - Zhiyun Wei
- Shanghai Key Laboratory of Maternal Fetal Medicine, Department of Women and Children's Health Care, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai 200092, China.
| | - Jing Hua
- Shanghai Key Laboratory of Maternal Fetal Medicine, Department of Women and Children's Health Care, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai 200092, China.
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Munir M, Setiawan H, Awaludin R, Kett VL. Aerosolised micro and nanoparticle: formulation and delivery method for lung imaging. Clin Transl Imaging 2023; 11:33-50. [PMID: 36196096 PMCID: PMC9521863 DOI: 10.1007/s40336-022-00527-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2022] [Accepted: 09/26/2022] [Indexed: 02/07/2023]
Abstract
Purpose The application of contrast and tracing agents is essential for lung imaging, as indicated by the wide use in recent decades and the discovery of various new contrast and tracing agents. Different aerosol production and pulmonary administration methods have been developed to improve lung imaging quality. This review details and discusses the ideal characteristics of aerosol administered via pulmonary delivery for lung imaging and the methods for the production and pulmonary administration of dry or liquid aerosol. Methods We explored several databases, including PubMed, Scopus, and Google Scholar, while preparing this review to discover and obtain the abstracts, reports, review articles, and research papers related to aerosol delivery for lung imaging and the formulation and pulmonary delivery method of dry and liquid aerosol. The search terms used were "dry aerosol delivery", "liquid aerosol delivery", "MRI for lung imaging", "CT scan for lung imaging", "SPECT for lung imaging", "PET for lung imaging", "magnetic particle imaging", "dry powder inhalation", "nebuliser", and "pressurised metered-dose inhaler". Results Through the literature review, we found that the critical considerations in aerosol delivery for lung imaging are appropriate lung deposition of inhaled aerosol and avoiding toxicity. The important tracing agent was also found to be Technetium-99m (99mTc), Gallium-68 (68Ga) and superparamagnetic iron oxide nanoparticle (SPION), while the essential contrast agents are gold, iodine, silver gadolinium, iron and manganese-based particles. The pulmonary delivery of such tracing and contrast agents can be performed using dry formulation (graphite ablation, spark ignition and spray dried powder) and liquid aerosol (nebulisation, pressurised metered-dose inhalation and air spray). Conclusion A dual-imaging modality with the combination of different tracing or contrast agents is a future development of aerosolised micro and nanoparticles for lung imaging to improve diagnosis success. Graphical abstract
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Affiliation(s)
- Miftakul Munir
- Research Center for Radioisotope Radiopharmaceutical and Biodosimetry Technology, National Research and Innovation Agency, South Tangerang, 15345 Indonesia
| | - Herlan Setiawan
- Research Center for Radioisotope Radiopharmaceutical and Biodosimetry Technology, National Research and Innovation Agency, South Tangerang, 15345 Indonesia
| | - Rohadi Awaludin
- Research Center for Radioisotope Radiopharmaceutical and Biodosimetry Technology, National Research and Innovation Agency, South Tangerang, 15345 Indonesia
| | - Vicky L. Kett
- School of Pharmacy, Queen’s University Belfast, 97 Lisburn Road, Belfast, BT9 7BL UK
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Cho HJ, Lee WS, Jeong J, Lee JS. A review on the impacts of nanomaterials on neuromodulation and neurological dysfunction using a zebrafish animal model. Comp Biochem Physiol C Toxicol Pharmacol 2022; 261:109428. [PMID: 35940544 DOI: 10.1016/j.cbpc.2022.109428] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/04/2022] [Revised: 07/28/2022] [Accepted: 08/03/2022] [Indexed: 11/20/2022]
Abstract
Nanomaterials have been widely employed from industrial to medical fields due to their small sizes and versatile characteristics. However, nanomaterials can also induce unexpected adverse effects on health. In particular, exposure of the nervous system to nanomaterials can cause serious neurological dysfunctions and neurodegenerative diseases. A number of studies have adopted various animal models to evaluate the neurotoxic effects of nanomaterials. Among them, zebrafish has become an attractive animal model for neurotoxicological studies due to several advantages, including the well-characterized nervous system, efficient genome editing, convenient generation of transgenic lines, high-resolution in vivo imaging, and an array of behavioral assays. In this review, we summarize recent studies on the neurotoxicological effects of nanomaterials, particularly engineered nanomaterials and nanoplastics, using zebrafish and discuss key findings with advantages and limitations of the zebrafish model in neurotoxicological studies.
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Affiliation(s)
- Hyun-Ju Cho
- Microbiome Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 125 Gwahak-ro, Yuseong-gu, Daejeon 34141, Republic of Korea
| | - Wang Sik Lee
- Environmental Disease Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 125 Gwahak-ro, Yuseong-gu, Daejeon 34141, Republic of Korea
| | - Jinyoung Jeong
- Environmental Disease Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 125 Gwahak-ro, Yuseong-gu, Daejeon 34141, Republic of Korea; KRIBB School, University of Science and Technology, Yuseong-gu, Daejeon, 34141, Republic of Korea.
| | - Jeong-Soo Lee
- Microbiome Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 125 Gwahak-ro, Yuseong-gu, Daejeon 34141, Republic of Korea; KRIBB School, University of Science and Technology, Yuseong-gu, Daejeon, 34141, Republic of Korea.
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Kumarasamy M, Tran N, Patarroyo J, Mishra S, Monopoli M, Madarasz E, Puntes V. “The Effects of Silver Nanoparticle Shape on Protein Adsorption and Neural Stem Cell Viability”. ChemistrySelect 2022. [DOI: 10.1002/slct.202201917] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
Affiliation(s)
- Murali Kumarasamy
- Department of Biotechnology National Institute of Pharmaceutical Education and Research (NIPER) Hajipur (Dept. of Pharmaceuticals, Ministry of Chemicals & Fertilizers, Govt. of India), Export Promotion Industrial Park (EPIP), Industrial Area Hajipur 844 102, District Vaishali, State Bihar India
- Laboratory of Cellular and Developmental Neurobiology Institute of Experimental Medicine of the Hungarian Academy of Sciences Budapest Hungary
| | - Ngoc Tran
- Catalan Institute of Nanoscience and Nanotechnology (ICN2), CSIC and BIST 08193 Barcelona Spain
- Department of Scientific Management Dong A University Da Nang Vietnam
| | - Javier Patarroyo
- Catalan Institute of Nanoscience and Nanotechnology (ICN2), CSIC and BIST 08193 Barcelona Spain
| | - Sushmita Mishra
- Department of Biotechnology National Institute of Pharmaceutical Education and Research (NIPER) Hajipur (Dept. of Pharmaceuticals, Ministry of Chemicals & Fertilizers, Govt. of India), Export Promotion Industrial Park (EPIP), Industrial Area Hajipur 844 102, District Vaishali, State Bihar India
| | - Marco Monopoli
- Centre for BioNano Interactions School of Chemistry and Chemical Biology and Conway Institute for Biomolecular and Biomedical Research University College Dublin, Belfield Dublin 4 Ireland
| | - Emilia Madarasz
- Laboratory of Cellular and Developmental Neurobiology Institute of Experimental Medicine of the Hungarian Academy of Sciences Budapest Hungary
| | - Victor Puntes
- Catalan Institute of Nanoscience and Nanotechnology (ICN2), CSIC and BIST 08193 Barcelona Spain
- Institució Catalana de Recerca i Estudis Avançats (ICREA) 08010 Barcelona Spain
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Huynh H, Upadhyay P, Lopez CH, Miyashiro MK, Van Winkle LS, Thomasy SM, Pinkerton KE. Inhalation of Silver Silicate Nanoparticles Leads to Transient and Differential Microglial Activation in the Rodent Olfactory Bulb. Toxicol Pathol 2022; 50:763-775. [PMID: 35768951 PMCID: PMC9529873 DOI: 10.1177/01926233221107607] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Engineered silver nanoparticles (AgNPs), including silver silicate nanoparticles (Ag-SiO2 NPs), are used in a wide variety of medical and consumer applications. Inhaled AgNPs have been found to translocate to the olfactory bulb (OB) after inhalation and intranasal instillation. However, the biological effects of Ag-SiO2 NPs and their potential nose-to-brain transport have not been evaluated. The present study assessed whether inhaled Ag-SiO2 NPs can elicit microglial activation in the OB. Adult Sprague-Dawley rats inhaled aerosolized Ag-SiO2 NPs at a concentration of 1 mg/ml for 6 hours. On day 0, 1, 7, and 21 post-exposure, rats were necropsied and OB were harvested. Immunohistochemistry on OB tissues were performed with anti-ionized calcium-binding adapter molecule 1 and heme oxygenase-1 as markers of microglial activation and oxidative stress, respectively. Aerosol characterization indicated Ag-SiO2 NPs were sufficiently aerosolized with moderate agglomeration and high-efficiency deposition in the nasal cavity and olfactory epithelium. Findings suggested that acute inhalation of Ag-SiO2 NPs elicited transient and differential microglial activation in the OB without significant microglial recruitment or oxidative stress. The delayed and differential pattern of microglial activation in the OB implied that inhaled Ag-SiO2 may have translocated to the central nervous system via intra-neuronal pathways.
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Affiliation(s)
- Huong Huynh
- William R Pritchard Veterinary Medical Teaching Hospital, University of California-Davis, Davis, CA, USA.,Center for Health and the Environment, University of California – Davis, Davis, CA, USA
| | - Priya Upadhyay
- Center for Health and the Environment, University of California – Davis, Davis, CA, USA
| | - Cora H Lopez
- Center for Health and the Environment, University of California – Davis, Davis, CA, USA
| | - Malia K Miyashiro
- Center for Health and the Environment, University of California – Davis, Davis, CA, USA
| | - Laura S Van Winkle
- Center for Health and the Environment, University of California – Davis, Davis, CA, USA.,Department of Anatomy, Physiology and Cell Biology, School of Veterinary Medicine, University of California – Davis, Davis, CA, USA
| | - Sara M Thomasy
- Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California - Davis, Davis, CA, USA.,Department of Ophthalmology and Vision Science, School of Medicine, University of California - Davis, Davis, CA, USA
| | - Kent E Pinkerton
- Center for Health and the Environment, University of California – Davis, Davis, CA, USA.,Department of Anatomy, Physiology and Cell Biology, School of Veterinary Medicine, University of California – Davis, Davis, CA, USA
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13
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O’Connell RC, Dodd TM, Clingerman SM, Fluharty KL, Coyle J, Stueckle TA, Porter DW, Bowers L, Stefaniak AB, Knepp AK, Derk R, Wolfarth M, Mercer RR, Boots TE, Sriram K, Hubbs AF. Developing a Solution for Nasal and Olfactory Transport of Nanomaterials. Toxicol Pathol 2022; 50:329-343. [PMID: 35416103 PMCID: PMC9872725 DOI: 10.1177/01926233221089209] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
Abstract
With advances in nanotechnology, engineered nanomaterial applications are a rapidly growing sector of the economy. Some nanomaterials can reach the brain through nose-to-brain transport. This transport creates concern for potential neurotoxicity of insoluble nanomaterials and a need for toxicity screening tests that detect nose-to-brain transport. Such tests can involve intranasal instillation of aqueous suspensions of nanomaterials in dispersion media that limit particle agglomeration. Unfortunately, protein and some elements in existing dispersion media are suboptimal for potential nose-to-brain transport of nanomaterials because olfactory transport has size- and ion-composition requirements. Therefore, we designed a protein-free dispersion media containing phospholipids and amino acids in an isotonic balanced electrolyte solution, a solution for nasal and olfactory transport (SNOT). SNOT disperses hexagonal boron nitride nanomaterials with a peak particle diameter below 100 nm. In addition, multiwalled carbon nanotubes (MWCNTs) in an established dispersion medium, when diluted with SNOT, maintain dispersion with reduced albumin concentration. Using stereomicroscopy and microscopic examination of plastic sections, dextran dyes dispersed in SNOT are demonstrated in the neuroepithelium of the nose and olfactory bulb of B6;129P2-Omptm3Mom/MomJ mice after intranasal instillation in SNOT. These findings support the potential for SNOT to disperse nanomaterials in a manner permitting nose-to-brain transport for neurotoxicity studies.
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Affiliation(s)
- Ryan C. O’Connell
- Centers for Disease Control and Prevention, Morgantown, West Virginia, USA,West Virginia University, Morgantown, West Virginia, USA
| | - Tiana M. Dodd
- Centers for Disease Control and Prevention, Morgantown, West Virginia, USA
| | | | - Kara L. Fluharty
- Centers for Disease Control and Prevention, Morgantown, West Virginia, USA
| | - Jayme Coyle
- Centers for Disease Control and Prevention, Morgantown, West Virginia, USA
| | - Todd A. Stueckle
- Centers for Disease Control and Prevention, Morgantown, West Virginia, USA
| | - Dale W. Porter
- Centers for Disease Control and Prevention, Morgantown, West Virginia, USA
| | - Lauren Bowers
- Centers for Disease Control and Prevention, Morgantown, West Virginia, USA
| | | | - Alycia K. Knepp
- Centers for Disease Control and Prevention, Morgantown, West Virginia, USA
| | - Raymond Derk
- Centers for Disease Control and Prevention, Morgantown, West Virginia, USA
| | - Michael Wolfarth
- Centers for Disease Control and Prevention, Morgantown, West Virginia, USA
| | - Robert R. Mercer
- Centers for Disease Control and Prevention, Morgantown, West Virginia, USA
| | - Theresa E. Boots
- Centers for Disease Control and Prevention, Morgantown, West Virginia, USA
| | - Krishnan Sriram
- Centers for Disease Control and Prevention, Morgantown, West Virginia, USA
| | - Ann F. Hubbs
- Centers for Disease Control and Prevention, Morgantown, West Virginia, USA
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14
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Liu N, Li Y, Liu L, Liu X, Yin Y, Qu G, Shi J, Song M, He B, Hu L, Jiang G. Administration of Silver Nasal Spray Leads to Nanoparticle Accumulation in Rat Brain Tissues. ENVIRONMENTAL SCIENCE & TECHNOLOGY 2022; 56:403-413. [PMID: 34923819 DOI: 10.1021/acs.est.1c02532] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/14/2023]
Abstract
The use of commercial products containing engineered nanomaterials in realistic scenarios may lead to the accumulation of exogenous particles in brain tissues. In this study, we simulated the use of silver (Ag) nasal spray in humans using Sprague-Dawley rats at 0.04 mg/kg/day. Silver-containing particles were explicitly identified in the rat brain after the administration of nasal sprays containing colloidal Ag or silver ions (Ag+) for 2 weeks using multiple methods. The accumulation of Ag-containing particles showed a delayed effect in different brain regions of the rats, with the mass concentration of particles increasing continuously for 1-2 weeks after the termination of administration. The size of the observed Ag-containing particles extracted from the brain tissues ranged from 18.3 to 120.4 nm. Further characterization by high-resolution transmission electron microscopy with energy-dispersive spectroscopy showed that the nanoparticles comprised both Ag and sulfur (S), with Ag/S atomic ratios of 1.1-7.1, suggesting that Ag-containing particles went through a series of transformations prior to or during their accumulation in the brain. Collectively, these findings provide evidence for the accumulation and transformation of Ag-containing particles in the rat brain, indicating a realistic risk to brain health resulting from the application of Ag-containing commercial products.
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Affiliation(s)
- Nian Liu
- State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China
- College of Resources and Environment, University of Chinese Academy of Sciences, Beijing 100049, China
- School of Environment, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou 310024, China
| | - Yu Li
- State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China
- College of Resources and Environment, University of Chinese Academy of Sciences, Beijing 100049, China
| | - Lihong Liu
- State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China
- College of Resources and Environment, University of Chinese Academy of Sciences, Beijing 100049, China
| | - Xiaolei Liu
- State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China
- College of Resources and Environment, University of Chinese Academy of Sciences, Beijing 100049, China
| | - Yongguang Yin
- State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China
- College of Resources and Environment, University of Chinese Academy of Sciences, Beijing 100049, China
| | - Guangbo Qu
- State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China
- College of Resources and Environment, University of Chinese Academy of Sciences, Beijing 100049, China
| | - Jianbo Shi
- State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China
- College of Resources and Environment, University of Chinese Academy of Sciences, Beijing 100049, China
| | - Maoyong Song
- State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China
- College of Resources and Environment, University of Chinese Academy of Sciences, Beijing 100049, China
| | - Bin He
- State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China
- College of Resources and Environment, University of Chinese Academy of Sciences, Beijing 100049, China
| | - Ligang Hu
- State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China
- College of Resources and Environment, University of Chinese Academy of Sciences, Beijing 100049, China
- Institute of Environment and Health, Jianghan University, Wuhan 430056, China
- School of Environment, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou 310024, China
| | - Guibin Jiang
- State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China
- College of Resources and Environment, University of Chinese Academy of Sciences, Beijing 100049, China
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15
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Liu N, Qu G, Wen R, Liu X, Wang Y, Gao J, Yin Y, Shi J, Zhou Q, He B, Hu L, Jiang G. Occurrence of Silver-containing Particles in Rat Brains upon Intranasal Exposure of Silver Nanoparticles. Metallomics 2022; 14:6496052. [PMID: 34982823 DOI: 10.1093/mtomcs/mfab077] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2021] [Accepted: 12/29/2021] [Indexed: 11/13/2022]
Abstract
The widespread application of silver nanomaterials raises health concerns due to the adverse effects that can be associated with silver nanoparticles (AgNPs) exposure. AgNPs can be introduced into human bodies via inhalation, either intentionally (intranasal administration of AgNPs) or unintentionally (environmental pollution, accidental release, or occupational exposure). Recent studies have shown that intranasal exposure of experimental animals to AgNPs can lead to the accumulation of silver (Ag) in brain tissues. However, there is little information available concerning what forms of Ag (particulate and ionic) exist in brain tissues. This study aimed to investigate whether particulate Ag exists in rat brains following intranasal exposure of AgNPs at 1 mg/kg/day using multiple analytical techniques. The results demonstrated that Ag-containing particles were presented in AgNPs-exposed rat brains, accounting for 20.2%- 68.1% of the total Ag. The mass concentrations of Ag-containing particles in brain tissues increased with exposure time but only decreased by 37.5% after elimination for 4 weeks upon exposure cessation. The size of Ag-containing particles identified in rat brains was larger than the original AgNPs. The Ag-containing particles identified in the rat brain were composed of multiple elements, including Ag, sulfur (S), selenium (Se) with atomic percentages of 45.8%, 37.5%, 16.7% respectively. The finding highlighted the occurrence and accumulation of transformed AgNPs containing S and Se in rat brains after intranasal exposure to AgNPs, implying potential risks for brain health.
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Affiliation(s)
- Nian Liu
- School of Environment, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou 310024, China.,State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center of Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China
| | - Guangbo Qu
- School of Environment, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou 310024, China.,State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center of Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China.,College of Resources and Environment, University of Chinese Academy of Sciences, Beijing 100049, China
| | - Ruoxi Wen
- State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center of Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China
| | - Xiaolei Liu
- State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center of Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China.,College of Resources and Environment, University of Chinese Academy of Sciences, Beijing 100049, China
| | - Yuanyuan Wang
- State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center of Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China.,College of Resources and Environment, University of Chinese Academy of Sciences, Beijing 100049, China
| | - Jie Gao
- School of Environment, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou 310024, China.,State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center of Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China
| | - Yongguang Yin
- School of Environment, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou 310024, China.,State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center of Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China.,College of Resources and Environment, University of Chinese Academy of Sciences, Beijing 100049, China
| | - Jianbo Shi
- School of Environment, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou 310024, China.,State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center of Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China.,College of Resources and Environment, University of Chinese Academy of Sciences, Beijing 100049, China
| | - Qunfang Zhou
- School of Environment, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou 310024, China.,State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center of Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China.,College of Resources and Environment, University of Chinese Academy of Sciences, Beijing 100049, China
| | - Bin He
- School of Environment, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou 310024, China.,State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center of Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China.,College of Resources and Environment, University of Chinese Academy of Sciences, Beijing 100049, China
| | - Ligang Hu
- School of Environment, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou 310024, China.,State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center of Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China.,College of Resources and Environment, University of Chinese Academy of Sciences, Beijing 100049, China
| | - Guibin Jiang
- School of Environment, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou 310024, China.,State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center of Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China.,College of Resources and Environment, University of Chinese Academy of Sciences, Beijing 100049, China
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16
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Ma X, Wang Z, Hu X, Chen J, Zhang H, Li X, Xie F, Xu J. Nanozyme catalysis-powered portable mini-drainage device enables real-time and universal weighing analysis of silver ions and silver nanoparticles. JOURNAL OF HAZARDOUS MATERIALS 2021; 415:125689. [PMID: 33773247 DOI: 10.1016/j.jhazmat.2021.125689] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/15/2020] [Revised: 02/05/2021] [Accepted: 03/15/2021] [Indexed: 06/12/2023]
Abstract
We introduce a real-time quantitative analytical method for universal silver ions (Ag(I)) and silver nanoparticles (AgNPs) analysis based on a portable nanozyme catalysis-powered portable mini-drainage device. The device is composed of three main glass containers with different specifications. The catalase mimic of ascorbic acid-coated platinum nanoparticles (AA-PtNPs) was used to provide the pumping power to drain water by catalyzing a gas-generation reaction, and the inhibition effect of Ag(I) on the catalytic activity of AA-PtNPs is adopted to connect the target detection event with the mini-drainage device. Experimental results reveal that the mass of the overflowed water is inversely proportional to the concentration of Ag(I) and AgNPs so that their quantitation can be accomplished via real-time weighing of the overflowed water. The importance is that without requiring advanced instruments, this device can quantify Ag(I) and AgNPs with a limit of detection (LOD) of 2.0 nM for Ag(I), and 3.8 pM for AgNPs within 30 min, respectively. The reliability and accuracy are comparable with the inductively coupled plasma optical emission spectrometer (ICP-OES). All these appealing features provide us a remarkable insight into the design of versatile portable devices with potential applications in in-situ environmental monitoring under remote areas and resource-limited settings.
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Affiliation(s)
- Xiaoming Ma
- School of Chemistry and Chemical Engineering, Gannan Normal University, Ganzhou 341000, PR China; State Key Laboratory of Chemo/Biosensing and Chemometrics, Hunan University, Changsha 410082, PR China
| | - Zhen Wang
- School of Chemistry and Chemical Engineering, Gannan Normal University, Ganzhou 341000, PR China
| | - Xuan Hu
- School of Chemistry and Chemical Engineering, Gannan Normal University, Ganzhou 341000, PR China
| | - Jinghua Chen
- School of Chemistry and Chemical Engineering, Gannan Normal University, Ganzhou 341000, PR China
| | - Huifang Zhang
- School of Chemistry and Chemical Engineering, Gannan Normal University, Ganzhou 341000, PR China
| | - Xun Li
- School of Chemistry and Chemical Engineering, Gannan Normal University, Ganzhou 341000, PR China
| | - Fengyan Xie
- Fujian Key Laboratory of Functional Marine Sensing Materials, Minjiang University, Fuzhou 350108, PR China
| | - Jianguo Xu
- School of Food and Biological Engineering, Hefei University of Technology, Hefei 230009, PR China; State Key Laboratory of Chemo/Biosensing and Chemometrics, Hunan University, Changsha 410082, PR China; Fujian Key Laboratory of Functional Marine Sensing Materials, Minjiang University, Fuzhou 350108, PR China.
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17
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Jankowska-Kieltyka M, Roman A, Nalepa I. The Air We Breathe: Air Pollution as a Prevalent Proinflammatory Stimulus Contributing to Neurodegeneration. Front Cell Neurosci 2021; 15:647643. [PMID: 34248501 PMCID: PMC8264767 DOI: 10.3389/fncel.2021.647643] [Citation(s) in RCA: 47] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2020] [Accepted: 06/02/2021] [Indexed: 12/12/2022] Open
Abstract
Air pollution is regarded as an important risk factor for many diseases that affect a large proportion of the human population. To date, accumulating reports have noted that particulate matter (PM) is closely associated with the course of cardiopulmonary disorders. As the incidence of Alzheimer’s disease (AD), Parkinson’s disease (PD), and autoimmune disorders have risen and as the world’s population is aging, there is an increasing interest in environmental health hazards, mainly air pollution, which has been slightly overlooked as one of many plausible detrimental stimuli contributing to neurodegenerative disease onset and progression. Epidemiological studies have indicated a noticeable association between exposure to PM and neurotoxicity, which has been gradually confirmed by in vivo and in vitro studies. After entering the body directly through the olfactory epithelium or indirectly by passing through the respiratory system into the circulatory system, air pollutants are subsequently able to reach the brain. Among the potential mechanisms underlying particle-induced detrimental effects in the periphery and the central nervous system (CNS), increased oxidative stress, inflammation, mitochondrial dysfunction, microglial activation, disturbance of protein homeostasis, and ultimately, neuronal death are often postulated and concomitantly coincide with the main pathomechanisms of neurodegenerative processes. Other complementary mechanisms by which PM could mediate neurotoxicity and contribute to neurodegeneration remain unconfirmed. Furthermore, the question of how strong and proven air pollutants are as substantial adverse factors for neurodegenerative disease etiologies remains unsolved. This review highlights research advances regarding the issue of PM with an emphasis on neurodegeneration markers, symptoms, and mechanisms by which air pollutants could mediate damage in the CNS. Poor air quality and insufficient knowledge regarding its toxicity justify conducting scientific investigations to understand the biological impact of PM in the context of various types of neurodegeneration.
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Affiliation(s)
- Monika Jankowska-Kieltyka
- Department of Brain Biochemistry, Maj Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland
| | - Adam Roman
- Department of Brain Biochemistry, Maj Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland
| | - Irena Nalepa
- Department of Brain Biochemistry, Maj Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland
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18
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Shang M, Chang X, Niu S, Li J, Zhang W, Wu T, Zhang T, Tang M, Xue Y. The key role of autophagy in silver nanoparticle-induced BV2 cells inflammation and polarization. Food Chem Toxicol 2021; 154:112324. [PMID: 34111491 DOI: 10.1016/j.fct.2021.112324] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2021] [Revised: 05/15/2021] [Accepted: 06/02/2021] [Indexed: 11/18/2022]
Abstract
As the release of silver nanoparticles (AgNPs) in the environment continues to increase, great concerns have been raised about their potential toxicity to humans. It is urgent to assess the possible toxicity of AgNPs to the immune cells of the central nervous system due to the continuous accumulation of AgNPs in the brain. This study aimed to evaluate the neurotoxicity of AgNPs and the regulatory mechanism of autophagy in AgNPs-induced inflammation by using mouse microglia BV2 cell lines. AgNPs decreased the microglia cell activity in a concentration and time-dependent manner. The exposure of BV2 cells to AgNPs at a non-cytotoxic level of 5 μg/mL resulted in increase of pro-inflammatory cytokines and decrease of mRNA expression of anti-inflammatory cytokines. AgNPs exposure increased M1 markers of iNOS expression and decreased the expression of M2 markers of CD206 in a time-dependent manner. Meanwhile, the expression of inflammatory proteins IL-1β and NF-κB increased significantly. Additionally, AgNPs induced an increase in autophagosome and upregulation of LC3II, Beclin1, and p62 expression levels. Pretreatment by an autophagy inhibitor, 3-Methyladenine, caused more AgNPs-treated microglia to polarized into pro-inflammatory phenotypes. Inhibition of autophagy also increased the expression of inflammation-associated mRNA and proteins in BV2 cells. These results indicated that AgNPs could induce pro-inflammatory phenotypic polarization of microglia and the autophagy could play a key regulatory role in the pro-inflammatory phenotypic polarization of microglia induced by AgNPs.
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Affiliation(s)
- Mengting Shang
- Key Laboratory of Environmental Medicine and Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, 210009, China
| | - Xiaoru Chang
- Key Laboratory of Environmental Medicine and Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, 210009, China
| | - Shuyan Niu
- Key Laboratory of Environmental Medicine and Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, 210009, China
| | - Jiangyan Li
- Key Laboratory of Environmental Medicine and Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, 210009, China
| | - Wenli Zhang
- Key Laboratory of Environmental Medicine and Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, 210009, China
| | - Tianshu Wu
- Key Laboratory of Environmental Medicine and Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, 210009, China
| | - Ting Zhang
- Key Laboratory of Environmental Medicine and Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, 210009, China
| | - Meng Tang
- Key Laboratory of Environmental Medicine and Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, 210009, China
| | - Yuying Xue
- Key Laboratory of Environmental Medicine and Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, 210009, China.
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19
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Chen Q, Ma Y, Bai P, Li Q, Canup BSB, Long D, Ke B, Dai F, Xiao B, Li C. Tumor Microenvironment-Responsive Nanococktails for Synergistic Enhancement of Cancer Treatment via Cascade Reactions. ACS APPLIED MATERIALS & INTERFACES 2021; 13:4861-4873. [PMID: 33471499 DOI: 10.1021/acsami.0c20268] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/12/2023]
Abstract
A combination treatment strategy that relies on the synergetic effects of different therapeutic approaches has been considered to be an effective method for cancer therapy. Herein, a chemotherapeutic drug (doxorubicin, Dox) and a manganese ion (Mn2+) were co-loaded into regenerated silk fibroin-based nanoparticles (NPs), followed by the surface conjugation of phycocyanin (PC) to construct tumor microenvironment-activated nanococktails. The resultant PC-Mn@Dox-NPs showed increased drug release rates by responding to various stimulating factors (acidic pH, hydrogen peroxide (H2O2), and glutathione), revealing that they could efficiently release the payloads (Dox and Mn2+) in tumor cells. The released Dox could not only inhibit the growth of tumor cells but also generated a large amount of H2O2. The elevated H2O2 was decomposed into the highly harmful hydroxyl radicals and oxygen through an Mn2+-mediated Fenton-like reaction. Furthermore, the generated oxygen participated in photodynamic therapy (PDT) and produced abundant singlet oxygen. Our investigations demonstrate that these PC-Mn@Dox-NPs exhibit multiple bioresponsibilities and favorable biosafety. By integrating Dox-induced chemotherapy, Mn2+-mediated chemodynamic therapy, and PC-based PDT via cascade reactions, PC-Mn@Dox-NPs achieved enhanced in vitro and in vivo anticancer efficacies compared to all the mono- or dual-therapeutic approaches. These findings reveal that PC-Mn@Dox-NPs can be exploited as a promising nanococktail for cascade reaction-mediated synergistic cancer treatment.
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Affiliation(s)
- Qiubing Chen
- Key Laboratory of Sericultural Biology and Genetic Breeding, Ministry of Agriculture and Rural Affairs, State Key Laboratory of Silkworm Genome Biology, College of Sericulture, Textile and Biomass Sciences, Southwest University, 2 Tiansheng Road, Beibei, Chongqing 400715, P. R. China
- Chongqing Key Laboratory of Soft-Matter Material Chemistry and Function Manufacturing, School of Materials and Energy, Southwest University, 2 Tiansheng Road, Beibei, Chongqing 400715, P. R. China
| | - Ya Ma
- Key Laboratory of Sericultural Biology and Genetic Breeding, Ministry of Agriculture and Rural Affairs, State Key Laboratory of Silkworm Genome Biology, College of Sericulture, Textile and Biomass Sciences, Southwest University, 2 Tiansheng Road, Beibei, Chongqing 400715, P. R. China
| | - Peng Bai
- Department of Forensic Genetics, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, 37 Guoxuexiang, Chengdu, Sichuan 610041, P. R. China
| | - Qian Li
- Chongqing Key Laboratory of Soft-Matter Material Chemistry and Function Manufacturing, School of Materials and Energy, Southwest University, 2 Tiansheng Road, Beibei, Chongqing 400715, P. R. China
| | - Brandon S B Canup
- Center for Diagnostics and Therapeutics, Georgia State University, 100 Piedmont Avenue, Atlanta, Georgia 30303, United States
| | - Dingpei Long
- Key Laboratory of Sericultural Biology and Genetic Breeding, Ministry of Agriculture and Rural Affairs, State Key Laboratory of Silkworm Genome Biology, College of Sericulture, Textile and Biomass Sciences, Southwest University, 2 Tiansheng Road, Beibei, Chongqing 400715, P. R. China
| | - Bowen Ke
- Department of Forensic Genetics, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, 37 Guoxuexiang, Chengdu, Sichuan 610041, P. R. China
| | - Fangyin Dai
- Key Laboratory of Sericultural Biology and Genetic Breeding, Ministry of Agriculture and Rural Affairs, State Key Laboratory of Silkworm Genome Biology, College of Sericulture, Textile and Biomass Sciences, Southwest University, 2 Tiansheng Road, Beibei, Chongqing 400715, P. R. China
| | - Bo Xiao
- Key Laboratory of Sericultural Biology and Genetic Breeding, Ministry of Agriculture and Rural Affairs, State Key Laboratory of Silkworm Genome Biology, College of Sericulture, Textile and Biomass Sciences, Southwest University, 2 Tiansheng Road, Beibei, Chongqing 400715, P. R. China
- Chongqing Key Laboratory of Soft-Matter Material Chemistry and Function Manufacturing, School of Materials and Energy, Southwest University, 2 Tiansheng Road, Beibei, Chongqing 400715, P. R. China
| | - Changming Li
- Chongqing Key Laboratory of Soft-Matter Material Chemistry and Function Manufacturing, School of Materials and Energy, Southwest University, 2 Tiansheng Road, Beibei, Chongqing 400715, P. R. China
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20
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Andrade-Oliva MDLA, Escamilla-Sánchez J, Debray-García Y, Morales-Rubio RA, González-Pantoja R, Uribe-Ramírez M, Amador-Muñoz O, Díaz-Godoy RV, De Vizcaya-Ruiz A, Arias-Montaño JA. In vitro exposure to ambient fine and ultrafine particles alters dopamine uptake and release, and D 2 receptor affinity and signaling. ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY 2020; 80:103484. [PMID: 32942001 DOI: 10.1016/j.etap.2020.103484] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/13/2020] [Revised: 08/20/2020] [Accepted: 08/25/2020] [Indexed: 06/11/2023]
Abstract
The exposure to environmental pollutants, such as fine and ultrafine particles (FP and UFP), has been associated with increased risk for Parkinson's disease, depression and schizophrenia, disorders related to altered dopaminergic transmission. The striatum, a neuronal nucleus with extensive dopaminergic afferents, is a target site for particle toxicity, which results in oxidative stress, inflammation, astrocyte activation and modifications in dopamine content and D2 receptor (D2R) density. In this study we assessed the in vitro effect of the exposure to FP and UFP on dopaminergic transmission, by evaluating [3H]-dopamine uptake and release by rat striatal isolated nerve terminals (synaptosomes), as well as modifications in the affinity and signaling of native and cloned D2Rs. FP and UFP collected from the air of Mexico City inhibited [3H]-dopamine uptake and increased depolarization-evoked [3H]-dopamine release in striatal synaptosomes. FP and UFP also enhanced D2R affinity for dopamine in membranes from either rat striatum or CHO-K1 cells transfected with the long isoform of the human D2R (hD2LR)2LR). In CHO-K1-hD2L In CHO-K1-hD2LR cells or striatal slices, FP and UFP increased the potency of dopamine or the D2R agonist quinpirole, respectively, to inhibit forskolin-induced cAMP formation. The effects were concentration-dependent, with UFP being more potent than FP. These results indicate that FP and UFP directly affect dopaminergic transmission.
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Affiliation(s)
- María-de-Los-Angeles Andrade-Oliva
- Departamento de Fisiología, Biofísica y Neurociencias, Centro de Investigación y de Estudios Avanzados (Cinvestav) del IPN, Av. IPN 2508, Zacatenco, 07360, Ciudad de México, Mexico
| | - Juan Escamilla-Sánchez
- Departamento de Fisiología, Biofísica y Neurociencias, Centro de Investigación y de Estudios Avanzados (Cinvestav) del IPN, Av. IPN 2508, Zacatenco, 07360, Ciudad de México, Mexico
| | - Yazmín Debray-García
- Departamento de Fisiología, Biofísica y Neurociencias, Centro de Investigación y de Estudios Avanzados (Cinvestav) del IPN, Av. IPN 2508, Zacatenco, 07360, Ciudad de México, Mexico; Departamento de Investigación en Inmunología y Medicina Ambiental, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Calzada de Tlalpan 4502, 14080, Ciudad de México, Mexico
| | - Russell A Morales-Rubio
- Departamento de Toxicología, Centro de Investigación y de Estudios Avanzados (Cinvestav) del IPN, Av. IPN 2508, Zacatenco, 07360, Ciudad de México, Mexico
| | - Raúl González-Pantoja
- Departamento de Fisiología, Biofísica y Neurociencias, Centro de Investigación y de Estudios Avanzados (Cinvestav) del IPN, Av. IPN 2508, Zacatenco, 07360, Ciudad de México, Mexico
| | - Marisela Uribe-Ramírez
- Departamento de Toxicología, Centro de Investigación y de Estudios Avanzados (Cinvestav) del IPN, Av. IPN 2508, Zacatenco, 07360, Ciudad de México, Mexico
| | - Omar Amador-Muñoz
- Centro de Ciencias de la Atmósfera, Universidad Nacional Autónoma de México, Investigación Científica s/n, Ciudad Universitaria, Coyoacán, 04510, Ciudad de México, Mexico
| | - Raúl V Díaz-Godoy
- Instituto Nacional de Investigaciones Nucleares, Carretera México Toluca s/n, La Marquesa, 52750, Ocoyoacac, Estado de México, Mexico
| | - Andrea De Vizcaya-Ruiz
- Departamento de Toxicología, Centro de Investigación y de Estudios Avanzados (Cinvestav) del IPN, Av. IPN 2508, Zacatenco, 07360, Ciudad de México, Mexico
| | - José-Antonio Arias-Montaño
- Departamento de Fisiología, Biofísica y Neurociencias, Centro de Investigación y de Estudios Avanzados (Cinvestav) del IPN, Av. IPN 2508, Zacatenco, 07360, Ciudad de México, Mexico.
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21
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Zhao N, Francis NL, Calvelli HR, Moghe PV. Microglia-targeting nanotherapeutics for neurodegenerative diseases. APL Bioeng 2020; 4:030902. [PMID: 32923843 PMCID: PMC7481010 DOI: 10.1063/5.0013178] [Citation(s) in RCA: 54] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2020] [Accepted: 08/07/2020] [Indexed: 12/14/2022] Open
Abstract
Advances in nanotechnology have enabled the design of nanotherapeutic platforms that could address the challenges of targeted delivery of active therapeutic agents to the central nervous system (CNS). While the majority of previous research studies on CNS nanotherapeutics have focused on neurons and endothelial cells, the predominant resident immune cells of the CNS, microglia, are also emerging as a promising cellular target for neurodegeneration considering their prominent role in neuroinflammation. Under normal physiological conditions, microglia protect neurons by removing pathological agents. However, long-term exposure of microglia to stimulants will cause sustained activation and lead to neuronal damage due to the release of pro-inflammatory agents, resulting in neuroinflammation and neurodegeneration. This Perspective highlights criteria to be considered when designing microglia-targeting nanotherapeutics for the treatment of neurodegenerative disorders. These criteria include conjugating specific microglial receptor-targeting ligands or peptides to the nanoparticle surface to achieve targeted delivery, leveraging microglial phagocytic properties, and utilizing biocompatible and biodegradable nanomaterials with low immune reactivity and neurotoxicity. In addition, certain therapeutic agents for the controlled inhibition of toxic protein aggregation and for modulation of microglial activation pathways can also be incorporated within the nanoparticle structure without compromising stability. Overall, considering the multifaceted disease mechanisms of neurodegeneration, microglia-targeted nanodrugs and nanotherapeutic particles may have the potential to resolve multiple pathological determinants of the disease and to guide a shift in the microglial phenotype spectrum toward a more neuroprotective state.
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Affiliation(s)
- Nanxia Zhao
- Department of Chemical and Biochemical Engineering, 98 Brett Rd., Rutgers University, Piscataway, New Jersey 08854, USA
| | - Nicola L. Francis
- Department of Biomedical Engineering, 599 Taylor Rd., Rutgers University, Piscataway, New Jersey 08854, USA
| | - Hannah R. Calvelli
- Department of Molecular Biology and Biochemistry, 604 Allison Rd., Rutgers University, Piscataway, New Jersey 08854, USA
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22
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Agans R, Dymond CE, Jimenez RE, Bunce NJ, Perry KJ, Salisbury RL, Hussain SM, Gupta RK, Karna SP. Human Nontumorigenic Microglia Synthesize Strongly Fluorescent Au/Fe Nanoclusters, Retaining Bioavailability. ACS OMEGA 2020; 5:20983-20990. [PMID: 32875234 PMCID: PMC7450618 DOI: 10.1021/acsomega.0c02455] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 05/25/2020] [Accepted: 07/10/2020] [Indexed: 06/11/2023]
Abstract
The ability for cells to self-synthesize metal-core nanoclusters (mcNCs) offers increased imaging and identification opportunities. To date, much work has been done illustrating the ability for human tumorigenic cell lines to synthesize mcNCs; however, this has not been illustrated for nontumorigenic cell lines. Here, we present the ability for human nontumorigenic microglial cells, which are the major immune cells in the central nervous system, to self-synthesize gold (Au) and iron (Fe) core nanoclusters, following exposures to metallic salts. We also show the ability for cells to internalize presynthesized Au and Fe mcNCs. Cellular fluorescence increased in most exposures and in a dose dependent manner in the case of Au salt. Scanning transmission electron microscopic imaging confirmed the presence of the metal within cells, while transmission electron microscopy images confirmed nanocluster structures and self-synthesis. Interestingly, self-synthesized nanoclusters were of similar size and internal structure as presynthesized mcNCs. Toxicity assessment of both salts and presynthesized NCs illustrated a lack of toxicity from Au salt and presynthesized NCs. However, Fe salt was generally more toxic and stressful to cells at similar concentrations.
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Affiliation(s)
- Richard
T. Agans
- Henry M. Jackson
Foundation for the Advancement of Military Medicine, Bethesda, Maryland 20187, United States
- Molecular
Mechanisms Branch, Human Centered ISR Division, Airman Systems Directorate, 711 Human Performance
Wing, AFRL, Wright
Patterson AFB, Ohio 45433, United States
| | - Cayley E. Dymond
- Molecular
Mechanisms Branch, Human Centered ISR Division, Airman Systems Directorate, 711 Human Performance
Wing, AFRL, Wright
Patterson AFB, Ohio 45433, United States
| | - Rebecca E. Jimenez
- CCDC Army Research Laboratory, Aberdeen Proving Ground, Maryland 21005, United
States
| | - Nile J. Bunce
- CCDC Army Research Laboratory, Aberdeen Proving Ground, Maryland 21005, United
States
| | - Karima J. Perry
- CCDC Army Research Laboratory, Aberdeen Proving Ground, Maryland 21005, United
States
| | - Richard L. Salisbury
- Henry M. Jackson
Foundation for the Advancement of Military Medicine, Bethesda, Maryland 20187, United States
- Molecular
Mechanisms Branch, Human Centered ISR Division, Airman Systems Directorate, 711 Human Performance
Wing, AFRL, Wright
Patterson AFB, Ohio 45433, United States
| | - Saber M. Hussain
- Molecular
Mechanisms Branch, Human Centered ISR Division, Airman Systems Directorate, 711 Human Performance
Wing, AFRL, Wright
Patterson AFB, Ohio 45433, United States
| | - Raj K. Gupta
- DoD Blast Injury Research Program Coordination Office, Medical Research and Development Command, Fort Detrick, Maryland 21702, United States
| | - Shashi P. Karna
- CCDC Army Research Laboratory, Aberdeen Proving Ground, Maryland 21005, United
States
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Wu T, Liang X, He K, Liu X, Li Y, Wang Y, Kong L, Tang M. The NLRP3-Mediated Neuroinflammatory Responses to CdTe Quantum Dots and the Protection of ZnS Shell. Int J Nanomedicine 2020; 15:3217-3233. [PMID: 32440120 PMCID: PMC7212783 DOI: 10.2147/ijn.s246578] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2020] [Accepted: 04/14/2020] [Indexed: 12/15/2022] Open
Abstract
Introduction Since CdTe quantum dots (QDs) are still widely considered as advanced fluorescent probes because of their far superior optical performance and fluorescence efficiency over non-cadmium QDs, it is important to find ways to control their toxicity. Methods In this study, the adverse effects of two cadmium-containing QDs, ie, CdTe QDs and CdTe@ZnS QDs, on the nervous system of nematode C. elegans, the hippocampus of mice, and cultured microglia were measured in order to evaluate the neuroinflammation caused by cadmium-containing QDs and the potential mechanisms. Results Firstly, we observed that cadmium-containing QD exposure-induced immune responses and neurobehavioral deficit in nematode C. elegans. In the mice treated with QDs, neuroinflammatory responses to QDs in the hippocampus, including microglial activation and IL-1ß release, occurred as well. When investigating the mechanisms of cadmium-containing QDs causing IL-1ß-mediated inflammation, the findings suggested that cadmium-containing QDs activated the NLRP3 inflammasome by causing excessive ROS generation, and resulted in IL-1ß release. Discussion Even though the milder immune responses and neurotoxicity of CdTe@ZnS QDs compared with CdTe QDs indicated the protective role of ZnS coating, the inhibitions of NLRP3 expression and ROS production completely reduced the IL-1ß-mediated inflammation. This provided valuable information that inhibiting target molecules is an effective and efficient way to alleviate the toxicity of cadmium-containing QDs, so it is important to evaluate QDs through a mechanism-based risk assessment.
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Affiliation(s)
- Tianshu Wu
- Key Laboratory of Environmental Medicine and Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, People's Republic of China
| | - Xue Liang
- Key Laboratory of Environmental Medicine and Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, People's Republic of China
| | - Keyu He
- Blood Transfusion Department, Zhongda Hospital, Southeast University, Nanjing 210009, People's Republic of China
| | - Xi Liu
- Key Laboratory of Environmental Medicine and Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, People's Republic of China
| | - Yimeng Li
- Key Laboratory of Environmental Medicine and Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, People's Republic of China
| | - Yutong Wang
- Key Laboratory of Environmental Medicine and Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, People's Republic of China
| | - Lu Kong
- Key Laboratory of Environmental Medicine and Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, People's Republic of China
| | - Meng Tang
- Key Laboratory of Environmental Medicine and Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, People's Republic of China
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24
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Islam SU, Shehzad A, Ahmed MB, Lee YS. Intranasal Delivery of Nanoformulations: A Potential Way of Treatment for Neurological Disorders. Molecules 2020; 25:molecules25081929. [PMID: 32326318 PMCID: PMC7221820 DOI: 10.3390/molecules25081929] [Citation(s) in RCA: 94] [Impact Index Per Article: 18.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2020] [Revised: 04/17/2020] [Accepted: 04/17/2020] [Indexed: 12/11/2022] Open
Abstract
Although the global prevalence of neurological disorders such as Parkinson’s disease, Alzheimer’s disease, glioblastoma, epilepsy, and multiple sclerosis is steadily increasing, effective delivery of drug molecules in therapeutic quantities to the central nervous system (CNS) is still lacking. The blood brain barrier (BBB) is the major obstacle for the entry of drugs into the brain, as it comprises a tight layer of endothelial cells surrounded by astrocyte foot processes that limit drugs’ entry. In recent times, intranasal drug delivery has emerged as a reliable method to bypass the BBB and treat neurological diseases. The intranasal route for drug delivery to the brain with both solution and particulate formulations has been demonstrated repeatedly in preclinical models, including in human trials. The key features determining the efficacy of drug delivery via the intranasal route include delivery to the olfactory area of the nares, a longer retention time at the nasal mucosal surface, enhanced penetration of the drugs through the nasal epithelia, and reduced drug metabolism in the nasal cavity. This review describes important neurological disorders, challenges in drug delivery to the disordered CNS, and new nasal delivery techniques designed to overcome these challenges and facilitate more efficient and targeted drug delivery. The potential for treatment possibilities with intranasal transfer of drugs will increase with the development of more effective formulations and delivery devices.
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Affiliation(s)
- Salman Ul Islam
- School of Life Sciences, College of Natural Sciences, Kyungpook National University, Daegu 41566, Korea; (S.U.I.); (M.B.A.)
| | - Adeeb Shehzad
- Department of Clinical Pharmacy, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman bin Faisal University, Dammam 31441, Saudi Arabia;
| | - Muhammad Bilal Ahmed
- School of Life Sciences, College of Natural Sciences, Kyungpook National University, Daegu 41566, Korea; (S.U.I.); (M.B.A.)
| | - Young Sup Lee
- School of Life Sciences, College of Natural Sciences, Kyungpook National University, Daegu 41566, Korea; (S.U.I.); (M.B.A.)
- Correspondence: ; Tel.: +82-53-950-6353; Fax: +82-53-943-2762
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25
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Neurotoxicity of nanoparticles entering the brain via sensory nerve-to-brain pathways: injuries and mechanisms. Arch Toxicol 2020; 94:1479-1495. [DOI: 10.1007/s00204-020-02701-w] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2020] [Accepted: 03/05/2020] [Indexed: 12/15/2022]
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26
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Wu T, Liang X, He K, Wei T, Wang Y, Zou L, Bai C, Liu N, Zhang T, Xue Y, Tang M. The role of NLRP3 inflammasome activation in the neuroinflammatory responses to Ag 2Se quantum dots in microglia. NANOSCALE 2019; 11:20820-20836. [PMID: 31657406 DOI: 10.1039/c9nr06778g] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/10/2023]
Abstract
Silver selenide quantum dots (Ag2Se QDs) provide bright prospects for the application of QDs in the field of biomedicine because they contain low-toxic compounds and show great advantages in the imaging of deep tissues and tiny vascular structures. However, the biosafety of these novel QDs has not been thoroughly evaluated, especially in one main target for toxicity-the central nervous system (CNS). Our previous studies have suggested severe inflammatory responses to cadmium-containing QDs in the hippocampus, which gives us a hint regarding the risk assessment of Ag2Se QDs. In this study, microglial activation followed by enhanced levels of pro-inflammatory cytokines was observed in the hippocampus of mice intravenously injected with Ag2Se QDs. When using the microglial BV2 cells to investigate the underlying mechanisms, we found that the NLRP3 inflammasome activation was involved in the IL-1β-mediated inflammation induced by Ag2Se QDs. On the one hand, Ag2Se QD-activated NF-κB participated in the NLRP3 inflammasome priming and assembly as well as the pro-IL-1β upregulation. On the other hand, Ag2Se QD-induced ROS generation, particularly mtROS, triggered the NLRP3 inflammasome activation and resulted in active caspase-1 to process pro-IL-1β into mature IL-1β release. These findings not only indicated that it is important to evaluate the biosafety of novel QDs, even those containing low-toxic compounds, but also provided an unbiased and mechanism-based risk assessment of similar nanoparticles.
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Affiliation(s)
- Tianshu Wu
- Key Laboratory of Environmental Medicine and Engineering, Ministry of Education; School of Public Health, Southeast University, Nanjing 210009, P.R. China.
| | - Xue Liang
- Key Laboratory of Environmental Medicine and Engineering, Ministry of Education; School of Public Health, Southeast University, Nanjing 210009, P.R. China.
| | - Keyu He
- Key Laboratory of Environmental Medicine and Engineering, Ministry of Education; School of Public Health, Southeast University, Nanjing 210009, P.R. China.
| | - Tingting Wei
- Key Laboratory of Environmental Medicine and Engineering, Ministry of Education; School of Public Health, Southeast University, Nanjing 210009, P.R. China.
| | - Yan Wang
- Key Laboratory of Environmental Medicine and Engineering, Ministry of Education; School of Public Health, Southeast University, Nanjing 210009, P.R. China.
| | - Lingyue Zou
- Key Laboratory of Environmental Medicine and Engineering, Ministry of Education; School of Public Health, Southeast University, Nanjing 210009, P.R. China.
| | - Changcun Bai
- Key Laboratory of Environmental Medicine and Engineering, Ministry of Education; School of Public Health, Southeast University, Nanjing 210009, P.R. China.
| | - Na Liu
- Key Laboratory of Environmental Medicine and Engineering, Ministry of Education; School of Public Health, Southeast University, Nanjing 210009, P.R. China.
| | - Ting Zhang
- Key Laboratory of Environmental Medicine and Engineering, Ministry of Education; School of Public Health, Southeast University, Nanjing 210009, P.R. China.
| | - Yuying Xue
- Key Laboratory of Environmental Medicine and Engineering, Ministry of Education; School of Public Health, Southeast University, Nanjing 210009, P.R. China.
| | - Meng Tang
- Key Laboratory of Environmental Medicine and Engineering, Ministry of Education; School of Public Health, Southeast University, Nanjing 210009, P.R. China.
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Abstract
OBJECTIVE Exposure to airborne particulate matter (PM) is estimated to cause millions of premature deaths annually. This work conveys known routes of exposure to PM and resultant health effects. METHODS A review of available literature. RESULTS Estimates for daily PM exposure are provided. Known mechanisms by which insoluble particles are transported and removed from the body are discussed. Biological effects of PM, including immune response, cytotoxicity, and mutagenicity, are reported. Epidemiological studies that outline the systemic health effects of PM are presented. CONCLUSION While the integrated, per capita, exposure of PM for a large fraction of the first-world may be less than 1 mg per day, links between several syndromes, including attention deficit hyperactivity disorder (ADHD), autism, loss of cognitive function, anxiety, asthma, chronic obstructive pulmonary disease (COPD), hypertension, stroke, and PM exposure have been suggested. This article reviews and summarizes such links reported in the literature.
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28
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Jahan I, George E, Saxena N, Sen S. Silver-Nanoparticle-Entrapped Soft GelMA Gels as Prospective Scaffolds for Wound Healing. ACS APPLIED BIO MATERIALS 2019; 2:1802-1814. [DOI: 10.1021/acsabm.8b00663] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
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Courtens F, Demangeat JL, Benabdallah M. Could the Olfactory System Be a Target for Homeopathic Remedies as Nanomedicines? J Altern Complement Med 2018; 24:1032-1038. [PMID: 29889551 PMCID: PMC6247980 DOI: 10.1089/acm.2018.0039] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023] Open
Abstract
Homeopathic remedies (HRs) contain odorant molecules such as flavonoids or terpenes and can lose their efficiency in presence of some competitive odors. Such similarities, along with extreme sensitivity of the olfactory system, widespread presence of olfactory receptors over all organic tissues (where they have metabolic roles besides perception of odors), and potential direct access to the brain through olfactory nerves (ONs) and trigeminal nerves, may suggest the olfactory system as target for HRs. Recent works highlighted that HRs exist in a dual form, that is, a still molecular form at low dilution and a nanoparticulate form at high dilution, and that remnants of source remedy persist in extremely high dilutions. From the literature, both odorants and nanoparticles (NPs) can enter the body through inhalation, digestive absorption, or through the skin, especially, NPs or viruses can directly reach the brain through axons of nerves. Assuming that HRs are recognized by olfactory receptors, their information could be transmitted to numerous tissues through receptor-ligand interaction, or to the brain by either activating the axon potential of ONs and trigeminal nerves or, in their nanoparticulate form, by translocating through axons of these nerves. Moreover, the nanoparticulate form may activate the immune system at multiple levels, induce systemic various biological responses through the pituitary axis and inflammation factors, or modulate gene expression at the cellular level. As immunity, inflammation, pituitary axis, and olfactory system are closely linked together, their permanent interaction triggered by olfactory receptors may thus ensure homeostasis.
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30
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Liang H, Chen A, Lai X, Liu J, Wu J, Kang Y, Wang X, Shao L. Neuroinflammation is induced by tongue-instilled ZnO nanoparticles via the Ca 2+-dependent NF-κB and MAPK pathways. Part Fibre Toxicol 2018; 15:39. [PMID: 30340606 PMCID: PMC6194560 DOI: 10.1186/s12989-018-0274-0] [Citation(s) in RCA: 62] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2018] [Accepted: 09/05/2018] [Indexed: 12/29/2022] Open
Abstract
Background The extensive biological applications of zinc oxide nanoparticles (ZnO NPs) in stomatology have created serious concerns about their biotoxicity. In our previous study, ZnO NPs were confirmed to transfer to the central nervous system (CNS) via the taste nerve pathway and cause neurodegeneration after 30 days of tongue instillation. However, the potential adverse effects on the brain caused by tongue-instilled ZnO NPs are not fully known. Methods In this study, the biodistribution of Zn, cerebral histopathology and inflammatory responses were analysed after 30 days of ZnO NPs tongue instillation. Moreover, the molecular mechanisms underlying neuroinflammation in vivo were further elucidated by treating BV2 and PC12 cells with ZnO NPs in vitro. Results This analysis indicated that ZnO NPs can transfer into the CNS, activate glial cells and cause neuroinflammation after tongue instillation. Furthermore, exposure to ZnO NPs led to a reduction in cell viability and induction of inflammatory response and calcium influx in BV2 and PC12 cells. The mechanism underlying how ZnO NPs induce neuroinflammation via the Ca2+-dependent NF-κB, ERK and p38 activation pathways was verified at the cytological level. Conclusion This study provided a new way how NPs, such as ZnO NPs, induce neuroinflammation via the taste nerve translocation pathway, a new mechanism for ZnO NPs-induced neuroinflammation and a new direction for nanomaterial toxicity analysis. Electronic supplementary material The online version of this article (10.1186/s12989-018-0274-0) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Huimin Liang
- Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.,Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering, Guangzhou, 510515, China
| | - Aijie Chen
- Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
| | - Xuan Lai
- Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
| | - Jia Liu
- Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
| | - Junrong Wu
- Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
| | - Yiyuan Kang
- Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
| | - Xinying Wang
- Zhujiang Hospital of Southern Medical University, Guangzhou, 510515, China
| | - Longquan Shao
- Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China. .,Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering, Guangzhou, 510515, China.
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31
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Weldon BA, Park JJ, Hong S, Workman T, Dills R, Lee JH, Griffith WC, Kavanagh TJ, Faustman EM. Using primary organotypic mouse midbrain cultures to examine developmental neurotoxicity of silver nanoparticles across two genetic strains. Toxicol Appl Pharmacol 2018; 354:215-224. [PMID: 29678449 DOI: 10.1016/j.taap.2018.04.017] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2017] [Revised: 04/10/2018] [Accepted: 04/13/2018] [Indexed: 11/19/2022]
Abstract
Micromass culture systems have been developed as three-dimensional organotypic in vitro alternatives to test developmental toxicity. We have optimized a murine-based embryonic midbrain micromass system in two genetic strains to evaluate neurodevelopmental effects of gold-cored silver nanoparticles (AgNPs) of differing sizes and coatings-20 nm AgCitrate, 110 nm AgCitrate, and 110 nm AgPVP. AgNPs are increasingly used in consumer, commercial, and medical products for their antimicrobial properties and observations of Ag in adult and fetal brain following in vivo exposures to AgNPs have led to concerns about the potential for AgNPs to elicit adverse effects on neurodevelopment and neurological function. Cytotoxicity was assessed at three time points of development by both nominal dose and by dosimetric dose. Ag dosimetry was assessed in cultures and the gold core component of the AgNPs was used as a tracer for determination of uptake of intact AgNPs and silver dissolution from particles in the culture system. Results by both nominal and dosimetric dose show cell death increased significantly in a dose-dependent manner at later time points (days 15 and 22 in vitro) that coincide with differentiation stages of development in both strains. When assessed by dosimetric dose, cultures were more sensitive to smaller particles, despite less uptake of Ag in smaller particles in both strains.
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Affiliation(s)
- Brittany A Weldon
- Institute for Risk Analysis and Risk Communication, University of Washington, Seattle, WA, USA; Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA, USA
| | - Julie Juyoung Park
- Institute for Risk Analysis and Risk Communication, University of Washington, Seattle, WA, USA; Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA, USA
| | - Sungwoo Hong
- Institute for Risk Analysis and Risk Communication, University of Washington, Seattle, WA, USA; Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA, USA
| | - Tomomi Workman
- Institute for Risk Analysis and Risk Communication, University of Washington, Seattle, WA, USA; Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA, USA
| | - Russell Dills
- Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA, USA
| | - Ji Hyun Lee
- Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA, USA
| | - William C Griffith
- Institute for Risk Analysis and Risk Communication, University of Washington, Seattle, WA, USA; Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA, USA
| | - Terrance J Kavanagh
- Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA, USA
| | - Elaine M Faustman
- Institute for Risk Analysis and Risk Communication, University of Washington, Seattle, WA, USA; Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA, USA.
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Ouyang S, Hu X, Zhou Q, Li X, Miao X, Zhou R. Nanocolloids in Natural Water: Isolation, Characterization, and Toxicity. ENVIRONMENTAL SCIENCE & TECHNOLOGY 2018; 52:4850-4860. [PMID: 29554418 DOI: 10.1021/acs.est.7b05364] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/08/2023]
Abstract
Nanocolloids are widespread in natural water systems, but their characterization and ecological risks are largely unknown. Herein, tangential flow ultrafiltration (TFU) was used to separate and concentrate nanocolloids from surface waters. Unexpectedly, nanocolloids were present in high concentrations ranging from 3.7 to 7.2 mg/L in the surface waters of the Harihe River in Tianjin City, China. Most of the nanocolloids were 10-40 nm in size, contained various trace metals and polycyclic aromatic hydrocarbons, and exhibited fluorescence properties. Envelopment effects and aggregation of Chlorella vulgaris in the presence of nanocolloids were observed. Nanocolloids entered cells and nanocolloid-exposed cells exhibited stronger plasmolysis, chloroplast damage and more starch grains than the control cells. Moreover, nanocolloids inhibited the cell growth, promoted reactive oxygen species (ROS), reduce the chlorophyll a content and increased the cell permeability. The genotoxicity of nanocolloids was also observed. The metabolomics analysis revealed a significant ( p < 0.05) downregulation of amino acids and upregulation of fatty acids contributing to ROS increase, chlorophyll a decrease and plasmolysis. The present work reveals that nanocolloids, which are different from specific, engineered nanoparticles (e.g., Ag nanoparticles), are present at high concentrations, exhibit an obvious toxicity in environments, and deserve more attention in the future.
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Affiliation(s)
- Shaohu Ouyang
- Key Laboratory of Pollution Processes and Environmental Criteria (Ministry of Education)/Tianjin Key Laboratory of Environmental Remediation and Pollution Control, College of Environmental Science and Engineering , Nankai University , Tianjin 300350 , China
| | - Xiangang Hu
- Key Laboratory of Pollution Processes and Environmental Criteria (Ministry of Education)/Tianjin Key Laboratory of Environmental Remediation and Pollution Control, College of Environmental Science and Engineering , Nankai University , Tianjin 300350 , China
| | - Qixing Zhou
- Key Laboratory of Pollution Processes and Environmental Criteria (Ministry of Education)/Tianjin Key Laboratory of Environmental Remediation and Pollution Control, College of Environmental Science and Engineering , Nankai University , Tianjin 300350 , China
| | - Xiaokang Li
- Key Laboratory of Pollution Processes and Environmental Criteria (Ministry of Education)/Tianjin Key Laboratory of Environmental Remediation and Pollution Control, College of Environmental Science and Engineering , Nankai University , Tianjin 300350 , China
| | - Xinyu Miao
- Key Laboratory of Pollution Processes and Environmental Criteria (Ministry of Education)/Tianjin Key Laboratory of Environmental Remediation and Pollution Control, College of Environmental Science and Engineering , Nankai University , Tianjin 300350 , China
| | - Ruiren Zhou
- Key Laboratory of Pollution Processes and Environmental Criteria (Ministry of Education)/Tianjin Key Laboratory of Environmental Remediation and Pollution Control, College of Environmental Science and Engineering , Nankai University , Tianjin 300350 , China
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Falconer JL, Alt JA, Grainger DW. Comparing ex vivo and in vitro translocation of silver nanoparticles and ions through human nasal epithelium. Biomaterials 2018; 171:97-106. [PMID: 29684679 DOI: 10.1016/j.biomaterials.2018.04.013] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2017] [Revised: 04/05/2018] [Accepted: 04/07/2018] [Indexed: 12/21/2022]
Abstract
Silver nanomaterials are widely used in clinically approved devices, consumer goods, and over-the-counter nutraceutical products. Despite the increase in silver nanomaterial research, few investigations have specifically distinguished the biological effects resulting from silver nanoparticles (AgNPs) versus silver ions released from AgNPs. This is in part, due to the complex analytical methods required to characterize silver ion release from AgNPs in biological media. This study sought to analyze silver ion release from AgNPs in biological media, compare silver transport from soluble AgNO3 and AgNPs through ex vivo full thickness sinus human tissue explants and human nasal epithelium and determine fractional AgNP internalization by human nasal epithelial cells. Rapid silver ion release is observed from AgNPs in human nasal epithelial cell medium over 3 h (9.6% of total silver mass). Significantly lower translocation of AgNPs is observed through human nasal epithelial cell monolayers and ex vivo human sinus tissue explants compared to silver ion (AgNO3). AgNP internalization is directly observed in AgNP-exposed human nasal epithelial cell monolayers by live cell scanning transmission electron microscopy (STEM), providing one potential mechanism for AgNP transcytosis. However, in vitro AgNP dissolution experiments suggest that silver in human nasal epithelium is primarily silver ion. Ionic AgNO3 produces significantly higher silver translocation, supporting previous results claiming silver ion as primarily responsible for biological effects of AgNPs.
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Affiliation(s)
- Jonathan L Falconer
- Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, USA.
| | - Jeremiah A Alt
- Division of Head and Neck Surgery, Rhinology - Sinus and Skull Base Surgery Program, Department of Surgery, University of Utah School of Medicine, USA.
| | - David W Grainger
- Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, USA; Department of Bioengineering, University of Utah, Salt Lake City, UT 84112, USA.
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Sun ZF, Gao X, Pinto JM, He Y, Yang Q, Tian J, Lv QW, Wei YX. Morphological evaluation using MRI of the olfactory filaments (fila) in a post-traumatic olfactory rat model. World J Otorhinolaryngol Head Neck Surg 2018; 4:50-56. [PMID: 30035262 PMCID: PMC6051302 DOI: 10.1016/j.wjorl.2018.03.004] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2018] [Accepted: 03/02/2018] [Indexed: 01/21/2023] Open
Abstract
OBJECTIVE To investigate whether magnetic resonance imaging (MRI) can be used to directly assess olfactory bulb (OB) lesions and quantify the associated morphological changes of olfactory filaments (OF), also known as fila, in an in vivo OB-lesion rat model of the brain. METHODS A surgical group (n = 5) of male Sprague-Dawley rats was subjected to the unilateral damage of the OB by a steel needle. The control group (n = 5) did not receive surgery. To assess olfactory system injury in vivo, T2-weighted MRI images were acquired in an oblique plane at a 30° angle from transverse plane one day after surgery. These brain regions were also assessed in the controls. The olfactory function was evaluated using the buried food pellet test (BFPT) 5 days before and after surgery. RESULTS The OF could be clearly observed on the MRI images from all animals. The left and right OF mean lengths (mm) were similar in the control group (0.81 ± 0.18 vs 0.89 ± 0.17, P > 0.05). In the surgical group, the OB was partially injured in all rats. These rats did not show differences in OF length between left- and right-side (0.83 ± 0.18 vs 0.93 ± 0.24, P > 0.05) at the time of measurement. The time (sec) required to find the food pellets in the BFPT was longer after than before the surgery (83.80 ± 34.37 vs 231.44 ± 53.23, P < 0.05). CONCLUSIONS MicroMRI may be a feasible tool to evaluate the OF and OBs in rat models. The unilateral partial OB lesion model appears to be an effective post-traumatic olfactory dysfunction model.
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Affiliation(s)
- Zhi-Fu Sun
- Department of Otorhinolaryngology Head and Neck Surgery, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China
| | - Xing Gao
- Department of Otorhinolaryngology Head and Neck Surgery, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China
| | - Jayant M. Pinto
- Section of Otolaryngology Head and Neck Surgery, Department of Surgery, The University of Chicago, Chicago, IL 60647, USA
| | - Yin He
- Department of Emergency, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China
| | - QingXian Yang
- Department of Radiology, Penn State College of Medicine, PA 17033, USA
| | - Jun Tian
- Department of Otorhinolaryngology Head and Neck Surgery, The First Hospital of Shanxi Medical University, Taiyuan 030001, China
| | - Qian-Wen Lv
- Department of Otorhinolaryngology Head and Neck Surgery, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China
| | - Yong-Xiang Wei
- Department of Otorhinolaryngology Head and Neck Surgery, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China
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Feng Y, He H, Li F, Lu Y, Qi J, Wu W. An update on the role of nanovehicles in nose-to-brain drug delivery. Drug Discov Today 2018; 23:1079-1088. [PMID: 29330120 DOI: 10.1016/j.drudis.2018.01.005] [Citation(s) in RCA: 79] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2017] [Revised: 11/16/2017] [Accepted: 01/04/2018] [Indexed: 12/28/2022]
Abstract
A quantitative analysis has cast doubt over the limited advantages provided by particles for nose-to-brain (NTB) drug delivery. Thus, it is imperative to identify the role of nanovehicles in NTB drug delivery. If nanocarriers are used merely as an option to improve various properties of the drugs or the formulations, it is difficult for them to outperform conventional formulations, such as solutions or gels. However, nanovehicles bring about special features, such as maintenance of the solubilized state of drugs, sustained or delayed release, and enhanced penetration because of surface modifications, all of which lead to enhanced NTB delivery efficiency.
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Affiliation(s)
- Yunhai Feng
- Department of Otorhinolaryngology Head & Neck Surgery, Dahua Hospital, Shanghai, China
| | - Haisheng He
- Key Laboratory of Smart Drug Delivery of MOE and PLA, School of Pharmacy, Fudan University, Shanghai, China
| | - Fengqian Li
- Department of Otorhinolaryngology Head & Neck Surgery, Dahua Hospital, Shanghai, China
| | - Yi Lu
- Key Laboratory of Smart Drug Delivery of MOE and PLA, School of Pharmacy, Fudan University, Shanghai, China
| | - Jianping Qi
- Key Laboratory of Smart Drug Delivery of MOE and PLA, School of Pharmacy, Fudan University, Shanghai, China
| | - Wei Wu
- Key Laboratory of Smart Drug Delivery of MOE and PLA, School of Pharmacy, Fudan University, Shanghai, China.
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Bencsik A, Lestaevel P, Guseva Canu I. Nano- and neurotoxicology: An emerging discipline. Prog Neurobiol 2018; 160:45-63. [DOI: 10.1016/j.pneurobio.2017.10.003] [Citation(s) in RCA: 44] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2017] [Revised: 09/10/2017] [Accepted: 10/20/2017] [Indexed: 12/12/2022]
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Vidanapathirana AK, Thompson LC, Herco M, Odom J, Sumner SJ, Fennell TR, Brown JM, Wingard CJ. Acute intravenous exposure to silver nanoparticles during pregnancy induces particle size and vehicle dependent changes in vascular tissue contractility in Sprague Dawley rats. Reprod Toxicol 2018; 75:10-22. [PMID: 29154916 PMCID: PMC6241519 DOI: 10.1016/j.reprotox.2017.11.002] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2017] [Revised: 10/26/2017] [Accepted: 11/13/2017] [Indexed: 12/17/2022]
Abstract
The use of silver nanoparticles (AgNP) raises safety concerns during susceptible life stages such as pregnancy. We hypothesized that acute intravenous exposure to AgNP during late stages of pregnancy will increase vascular tissue contractility, potentially contributing to alterations in fetal growth. Sprague Dawley rats were exposed to a single dose of PVP or Citrate stabilized 20 or 110nm AgNP (700μg/kg). Differential vascular responses and EC50 values were observed in myographic studies in uterine, mesenteric arteries and thoracic aortic segments, 24h post-exposure. Reciprocal responses were observed in aortic and uterine vessels following PVP stabilized AgNP with an increased force of contraction in uterine artery and increased relaxation responses in aorta. Citrate stabilized AgNP exposure increased contractile force in both uterine and aortic vessels. Intravenous AgNP exposure during pregnancy displayed particle size and vehicle dependent moderate changes in vascular tissue contractility, potentially influencing fetal blood supply.
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Affiliation(s)
- A K Vidanapathirana
- Department of Physiology, Brody School of Medicine, East Carolina University, Greenville, NC, 27834, USA
| | - L C Thompson
- Department of Physiology, Brody School of Medicine, East Carolina University, Greenville, NC, 27834, USA
| | - M Herco
- Department of Physiology, Brody School of Medicine, East Carolina University, Greenville, NC, 27834, USA
| | - J Odom
- Department of Physiology, Brody School of Medicine, East Carolina University, Greenville, NC, 27834, USA
| | - S J Sumner
- Discovery Sciences, RTI International, Research Triangle Park, NC, 27709, USA; Department of Nutrition School of Public Health University of North Carolina at Chapel Hill, Kannapolis, NC, 28081, USA
| | - T R Fennell
- Discovery Sciences, RTI International, Research Triangle Park, NC, 27709, USA
| | - J M Brown
- Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, CO, 80045, USA
| | - C J Wingard
- Department of Physiology, Brody School of Medicine, East Carolina University, Greenville, NC, 27834, USA; Department of Physical Therapy, Bellarmine University, Louisville, KY, 40205, USA.
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Maguire G. Amyotrophic lateral sclerosis as a protein level, non-genomic disease: Therapy with S2RM exosome released molecules. World J Stem Cells 2017; 9:187-202. [PMID: 29312526 PMCID: PMC5745587 DOI: 10.4252/wjsc.v9.i11.187] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2017] [Revised: 08/10/2017] [Accepted: 09/04/2017] [Indexed: 02/06/2023] Open
Abstract
Amyotrophic lateral sclerosis (ALS) is a rapidly progressing neurodegenerative disease that leads to death. No effective treatments are currently available. Based on data from epidemiological, etiological, laboratory, and clinical studies, I offer a new way of thinking about ALS and its treatment. This paper describes a host of extrinsic factors, including the exposome, that disrupt the extracellular matrix and protein function such that a spreading, prion-like disease leads to neurodegeneration in the motor tracts. A treatment regimen is described using the stem cell released molecules from a number of types of adult stem cells to provide tissue dependent molecules that restore homeostasis, including proteostasis, in the ALS patient. Because stem cells themselves as a therapeutic are cumbersome and expensive, and when implanted in a host cause aging of the host tissue and often fail to engraft or remain viable, only the S2RM molecules are used. Rebuilding of the extracellular matrix and repair of the dysfunctional proteins in the ALS patient ensues.
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Affiliation(s)
- Greg Maguire
- BioRegenerative Sciences, Inc., La Jolla, CA 92037, United States
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39
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Hopkins LE, Laing EA, Peake JL, Uyeminami D, Mack SM, Li X, Smiley-Jewell S, Pinkerton KE. Repeated Iron-Soot Exposure and Nose-to-brain Transport of Inhaled Ultrafine Particles. Toxicol Pathol 2017; 46:75-84. [PMID: 28914166 DOI: 10.1177/0192623317729222] [Citation(s) in RCA: 51] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Particulate exposure has been implicated in the development of a number of neurological maladies such as multiple sclerosis, amyotrophic lateral sclerosis, Alzheimer's disease, and idiopathic Parkinson's disease. Only a few studies have focused on the olfactory pathway as a portal through which combustion-generated particles may enter the brain. The primary objective of this study was to define the deposition, uptake, and transport of inhaled ultrafine iron-soot particles in the nasal cavities of mice to determine whether combustion-generated nanoparticles reach the olfactory bulb via the olfactory epithelium and nerve fascicles. Adult female C57B6 mice were exposed to iron-soot combustion particles at a concentration of 200 μg/m3, which included 40 μg/m3 of iron oxide nanoparticles. Mice were exposed for 6 hr/day, 5 days/week for 5 consecutive weeks (25 total exposure days). Our findings visually demonstrate that inhaled ultrafine iron-soot reached the brain via the olfactory nerves and was associated with indicators of neural inflammation.
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Affiliation(s)
- Laurie E Hopkins
- 1 Center for Health and the Environment, University of California, Davis, Davis, California, USA
| | - Emilia A Laing
- 1 Center for Health and the Environment, University of California, Davis, Davis, California, USA
| | - Janice L Peake
- 1 Center for Health and the Environment, University of California, Davis, Davis, California, USA
| | - Dale Uyeminami
- 1 Center for Health and the Environment, University of California, Davis, Davis, California, USA
| | - Savannah M Mack
- 1 Center for Health and the Environment, University of California, Davis, Davis, California, USA
| | - Xueting Li
- 1 Center for Health and the Environment, University of California, Davis, Davis, California, USA.,2 Institute of Human Nutrition, Columbia University, New York, New York, USA
| | - Suzette Smiley-Jewell
- 1 Center for Health and the Environment, University of California, Davis, Davis, California, USA
| | - Kent E Pinkerton
- 1 Center for Health and the Environment, University of California, Davis, Davis, California, USA
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40
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Picca RA, Paladini F, Sportelli MC, Pollini M, Giannossa LC, Di Franco C, Panico A, Mangone A, Valentini A, Cioffi N. Combined Approach for the Development of Efficient and Safe Nanoantimicrobials: The Case of Nanosilver-Modified Polyurethane Foams. ACS Biomater Sci Eng 2016; 3:1417-1425. [DOI: 10.1021/acsbiomaterials.6b00597] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Affiliation(s)
- Rosaria Anna Picca
- Dipartimento
di Chimica, Università degli Studi di Bari Aldo Moro, Via Orabona 4, 70126 Bari, Italy
| | - Federica Paladini
- Dipartimento
di Ingegneria dell’Innovazione, Università del Salento, Via per
Monteroni, 73100 Lecce, Italy
| | - Maria Chiara Sportelli
- Dipartimento
di Chimica, Università degli Studi di Bari Aldo Moro, Via Orabona 4, 70126 Bari, Italy
| | - Mauro Pollini
- Dipartimento
di Ingegneria dell’Innovazione, Università del Salento, Via per
Monteroni, 73100 Lecce, Italy
| | - Lorena Carla Giannossa
- Dipartimento
di Chimica, Università degli Studi di Bari Aldo Moro, Via Orabona 4, 70126 Bari, Italy
| | - Cinzia Di Franco
- CNR-IFN
- Dipartimento Interateneo di Fisica, Università degli Studi di Bari Aldo Moro, Via Amendola 173, 70126 Bari, Italy
| | - Angelica Panico
- Dipartimento
di Ingegneria dell’Innovazione, Università del Salento, Via per
Monteroni, 73100 Lecce, Italy
| | - Annarosa Mangone
- Dipartimento
di Chimica, Università degli Studi di Bari Aldo Moro, Via Orabona 4, 70126 Bari, Italy
| | - Antonio Valentini
- Dipartimento
Interateneo di Fisica, Università degli Studi di Bari Aldo Moro, Via Amendola 173, 70126 Bari, Italy
| | - Nicola Cioffi
- Dipartimento
di Chimica, Università degli Studi di Bari Aldo Moro, Via Orabona 4, 70126 Bari, Italy
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Calderón-Garcidueñas L. Smoking and Cerebral Oxidative Stress and Air Pollution: A Dreadful Equation with Particulate Matter Involved and One More Powerful Reason Not to Smoke Anything! J Alzheimers Dis 2016; 54:109-12. [PMID: 27447427 DOI: 10.3233/jad-160510] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Smoking has serious health effects. Cigarettes, including tobacco, marijuana, and electronic nicotine delivery systems are very effective ways to inhale harmful amounts of fine and ultrafine particulate matter. Does size matter? Yes, indeed! The smaller the particle you inhale, the higher the ability to produce reactive oxygen species and to readily access the brain. In this issue of the Journal of Alzheimer's Disease, Durazzo provides evidence of an association between active cigarette tobacco smoking in cognitively-normal elders and increased cerebral oxidative stress, while in actively smoking Alzheimer's disease (AD) patients, the association was also seen with smaller left and total hippocampal volumes. This paper has highly relevant results of interest across the US and the world because millions of people are active smokers and they have other genetic and environmental risk factors that could play a key role in the development/worsening of brain oxidative stress and neurodegeneration. Smoking basically anything producing aerosols with particulate matter in the fine and ultrafine size range is detrimental to your brain. Marijuana and e-cigarette use has grown steadily among adolescents and young adults. Smoking-related cerebral oxidative stress is a potential mechanism promoting AD pathology and increased risk for AD. Current knowledge also relates fine and ultrafine particles exposures influencing neurodevelopmental processes in utero. The results from Durazzo et al. should be put in a broader context, a context that includes evaluating the oxidative stress of nano-aerosols associated with cigarette emissions and their synergistic effects with air pollution exposures. AD is expected to increase in the US threefold by the year 2050, and some of these future AD patients are smoking and vaping right now. Understanding the impact of everyday exposures to long-term harmful consequences for brain health is imperative.
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Heusinkveld HJ, Wahle T, Campbell A, Westerink RHS, Tran L, Johnston H, Stone V, Cassee FR, Schins RPF. Neurodegenerative and neurological disorders by small inhaled particles. Neurotoxicology 2016; 56:94-106. [PMID: 27448464 DOI: 10.1016/j.neuro.2016.07.007] [Citation(s) in RCA: 219] [Impact Index Per Article: 24.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2016] [Revised: 07/18/2016] [Accepted: 07/18/2016] [Indexed: 12/17/2022]
Abstract
The world's population is steadily ageing and as a result, health conditions related to ageing, such as dementia, have become a major public health concern. In 2001, it was estimated that there were almost 5 million Europeans suffering from Alzheimer's disease (AD) and this figure has been projected to almost double by 2040. About 40% of people over 85 suffer from AD, and another 10% from Parkinson's disease (PD). The majority of AD and PD cases are of sporadic origin and environmental factors play an important role in the aetiology. Epidemiological research identified airborne particulate matter (PM) as one of the environmental factors potentially involved in AD and PD pathogenesis. Also, cumulating evidence demonstrates that the smallest sizes of the inhalable fraction of ambient particulate matter, also referred to as ultrafine particulate matter or nano-sized particles, are capable of inducing effects beyond the respiratory system. Translocation of very small particles via the olfactory epithelium in the nose or via uptake into the circulation has been demonstrated through experimental rodent studies with engineered nanoparticles. Outdoor air pollution has been linked to several health effects including oxidative stress and neuroinflammation that may ultimately result in neurodegeneration and cognitive impairment. This review aims to evaluate the relationship between exposure to inhaled ambient particles and neurodegeneration.
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Affiliation(s)
- Harm J Heusinkveld
- IUF-Leibniz Research Institute for Environmental Medicine, Düsseldorf, Germany; National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands, The Netherlands; AIR pollutants and Brain Aging research Group.
| | - Tina Wahle
- IUF-Leibniz Research Institute for Environmental Medicine, Düsseldorf, Germany; AIR pollutants and Brain Aging research Group
| | - Arezoo Campbell
- College of Pharmacy, Western University of Health Sciences, Pomona, CA, USA
| | - Remco H S Westerink
- Institute for Risk Assessment Sciences, Utrecht University, Utrecht, The Netherlands
| | - Lang Tran
- Institute of Occupational Medicine, Edinburgh, UK
| | | | - Vicki Stone
- Heriot-Watt University, School of Life Sciences, Edinburgh, UK
| | - Flemming R Cassee
- National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands, The Netherlands; Institute for Risk Assessment Sciences, Utrecht University, Utrecht, The Netherlands; AIR pollutants and Brain Aging research Group
| | - Roel P F Schins
- IUF-Leibniz Research Institute for Environmental Medicine, Düsseldorf, Germany; AIR pollutants and Brain Aging research Group
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