|
1
|
Xuan J, Hou S, Han Y, Li C, Liu Y, Li Z, Liu X, Yang G, Liu X, Wang J, Huang Y, Wang J, Lai W. Layer-Restacked 3D Ti 3C 2 Nanostructures with Efficient Photothermal Antibacterial Activities. ACS APPLIED BIO MATERIALS 2025; 8:3824-3832. [PMID: 40275489 DOI: 10.1021/acsabm.4c01997] [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] [Indexed: 04/26/2025]
Abstract
Multidrug-resistant bacterial infections have emerged as a global public health crisis due to antibiotic misuse. In this study, we develop a layer-restacked 3D Ti3C2 nanostructure utilizing ice-templating. This nanostructure exhibits outstanding hydrophilicity, biocompatibility, and stability, as well as enhanced absorption, extinction coefficient, and photothermal conversion efficiency. Additionally, the layer-restacked 3D Ti3C2 nanostructure demonstrates excellent antibacterial activity against MDR Escherichia coli and MDR Staphylococcus aureus irradiated by 808 nm near-infrared light (NIR). Specifically, the mechanism of photothermal action against multidrug-resistant bacteria involves structural damage to the bacterial membranes, leading to the leakage of bacterial contents after layer-restacked 3D Ti3C2 nanostructures adhered under NIR irradiation. The results of transcriptome analysis show that the 3D Ti3C2 nanostructure regulates the membrane transporters and membrane transporter proteins on the bacterial cell membrane as well as the activities of enzymes associated with them, which in turn affect the metabolic processes of organic acids and other organic substances in the bacterial cell. The DNA-binding transcriptional activator EvgA is significantly downregulated, which may play a crucial role in inhibiting the emergence of drug resistance in bacteria when exposed to the layer-restacked 3D Ti3C2 nanostructure. The layer-restacked 3D Ti3C2 nanostructure is an effective photothermal antimicrobial nanostructure against multidrug-resistant bacteria.
Collapse
Affiliation(s)
- Jinnan Xuan
- Hubei Key Laboratory of Photoelectric Materials and Devices, School of Materials Science and Engineering, Hubei Normal University, 11 Cihu Road, Huangshi 435002, P. R. China
- Laboratory of Solid State Microstructures, Nanjing University, Nanjing 210093, P. R. China
| | - Shuxian Hou
- College of Biological and Food Engineering, Anhui Polytechnic University, Wuhu 241000, P. R. China
| | - Yuqiang Han
- Hubei Key Laboratory of Photoelectric Materials and Devices, School of Materials Science and Engineering, Hubei Normal University, 11 Cihu Road, Huangshi 435002, P. R. China
| | - Chen Li
- Laboratory of Solid State Microstructures, Nanjing University, Nanjing 210093, P. R. China
| | - Yisi Liu
- Hubei Key Laboratory of Photoelectric Materials and Devices, School of Materials Science and Engineering, Hubei Normal University, 11 Cihu Road, Huangshi 435002, P. R. China
| | - Zhong Li
- Hubei Key Laboratory of Photoelectric Materials and Devices, School of Materials Science and Engineering, Hubei Normal University, 11 Cihu Road, Huangshi 435002, P. R. China
| | - Xixia Liu
- Hubei Key Laboratory of Edible Wild Plants Conservation and Utilization; Hubei Engineering Research Center of Special Wild Vegetables Breeding and Comprehensive Utilization Technology, Hubei Normal University, 11 Cihu Road, Huangshi 435002, Hubei Province, P. R. China
| | - Guoqiang Yang
- College of Biological and Food Engineering, Anhui Polytechnic University, Wuhu 241000, P. R. China
| | - Xinxin Liu
- College of Biological and Food Engineering, Anhui Polytechnic University, Wuhu 241000, P. R. China
| | - Jiantao Wang
- College of Biological and Food Engineering, Anhui Polytechnic University, Wuhu 241000, P. R. China
| | - Yuting Huang
- Department of Radiotherapy, Chaohu Hospital of Anhui Medical University, 64 Chaohu North Road, Chaohu 238000, P. R. China
| | - Jun Wang
- College of Biological and Food Engineering, Anhui Polytechnic University, Wuhu 241000, P. R. China
- Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing 211166, P. R. China
| | - Wei Lai
- Hubei Key Laboratory of Energy Storage and Power Battery, School of Mathematics, Physics and Optoelectronic Engineering, Hubei University of Automotive Technology, Shiyan 442002, P. R. China
| |
Collapse
|
|
2
|
Wang S, Yang J, Zhen C, Wang H, Shang P. Electromagnetic fields regulate iron metabolism: From mechanisms to applications. J Adv Res 2025:S2090-1232(25)00288-7. [PMID: 40311754 DOI: 10.1016/j.jare.2025.04.044] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2024] [Revised: 04/06/2025] [Accepted: 04/28/2025] [Indexed: 05/03/2025] Open
Abstract
BACKGROUND Electromagnetic fields (EMFs), as a form of physical therapy, have been widely applied in biomedicine. Iron, the most abundant trace metal in living organisms, plays a critical role in various physiological processes, and imbalances in its metabolism are closely associated with the development and progression of numerous diseases. Numerous studies have demonstrated that EMF exposureinduces significant changes in both systemic and cellular iron metabolism. AIM OF REVIEW This review aims to summarize the evidence and potential biophysical mechanisms underlying the role of EMFs in regulating iron metabolism, thereby enhancing the understanding of their biological mechanisms and expanding their potential applications in biomedical fields. KEY SCIENTIFIC CONCEPTS OF REVIEW In this review, we have synthesized research findings and proposed the hypothesis that the biophysical mechanisms of EMFs regulate iron metabolism involve the special electromagnetic properties of iron-containing proteins and iron-enriched tissues, as well as the modulation of membrane structure and function, ion channels, and the generation and activity of Reactive Oxygen Species (ROS). Then, the review summarizes the latest advances in the effects of EMFs on iron metabolism and their safety, as well as their impact on immunoregulation, cardiovascular diseases, neurological diseases, orthopedic diseases, diabetes, liver injury, and cancer.
Collapse
Affiliation(s)
- Shenghang Wang
- Department of Spine Surgery, People's Hospital of Longhua, Shenzhen, China; Research & Development Institute of Northwestern Polytechnical University in Shenzhen, Shenzhen, China
| | - Jiancheng Yang
- Department of Osteoporosis, Honghui Hospital, Xi'an Jiaotong University, Xi'an, China
| | - Chenxiao Zhen
- Department of Spine Surgery, People's Hospital of Longhua, Shenzhen, China; Research & Development Institute of Northwestern Polytechnical University in Shenzhen, Shenzhen, China; School of Life Sciences, Northwestern Polytechnical University, Xi'an, China
| | - Huiru Wang
- Research & Development Institute of Northwestern Polytechnical University in Shenzhen, Shenzhen, China; School of Life Sciences, Northwestern Polytechnical University, Xi'an, China
| | - Peng Shang
- Research & Development Institute of Northwestern Polytechnical University in Shenzhen, Shenzhen, China.
| |
Collapse
|
|
3
|
Li H, Tang S, Jia X, Zhu X, Cai L, Duan M, Wang S, Jiang H, Ji M, Wang S, Chen J. Combined toxicity evaluation of polystyrene nanoplastics and Nano-ZnO of distinctive morphology on human lung epithelial cells. THE SCIENCE OF THE TOTAL ENVIRONMENT 2025; 973:179097. [PMID: 40112547 DOI: 10.1016/j.scitotenv.2025.179097] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/23/2024] [Revised: 02/19/2025] [Accepted: 03/09/2025] [Indexed: 03/22/2025]
Abstract
Despite increasing concerns on the co-exposure of nanoplastics (NPs) and heavy metals including zinc oxide nanoparticles (Nano-ZnO) in the public health, the systematic studies as well as available methodology of combined toxicity evaluation of Nano-ZnO/NPs are lacking. In this study, the single and combined toxicity of Nano-ZnO and polystyrene nanoplastics (PS-NPs) on human lung epithelial cells were evaluated by a combination of in vitro approach including real-time cell analysis (RTCA), cell counting kit-8 (CCK-8), oxidative stress, cell membrane integrity and apoptosis assay. RTCA was employed to dynamically monitor the effect of combined exposure of Nano-ZnO and PS-NPs on cell growth, in comparison with end-point CCK-8 assay. It was found that the cytotoxicity of different Nano-ZnO involved disintegration of cell membrane and causing oxidative stress and apoptosis while PS-NPs mainly induced oxidative stress and apoptosis. The proposed study not only pinpointed the distinctive interaction mode between Nano-ZnO and nanoplastics, but provided integrated approaches to environment and health risk assessment of co-exposed Nano-ZnO and nanoplastics.
Collapse
Affiliation(s)
- Henghui Li
- Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing 211166, China
| | - Simin Tang
- Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing 211166, China
| | - Xiaoyu Jia
- Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing 211166, China
| | - Xinyi Zhu
- Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing 211166, China
| | - Ling Cai
- Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing 211166, China; School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189, China
| | - Mingxiu Duan
- Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing 211166, China
| | - Shaozhuo Wang
- Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing 211166, China
| | - Huijun Jiang
- School of Pharmacy, Nanjing Medical University, 211166 Nanjing, China
| | - MingHui Ji
- School of Nursing, Nanjing Medical University, Nanjing 211166, China
| | - Shoulin Wang
- Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
| | - Jin Chen
- Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing 211166, China; School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189, China; Jiangsu Province Engineering Research Center of Antibody Drug, Key Laboratory of Antibody Technique of National Health Commission, Nanjing Medical University, Nanjing 211166, China.
| |
Collapse
|
|
4
|
Patne AY, Mohapatra S, Mohapatra SS. Role of Nanomedicine in Transforming Pharmacotherapy for Substance Use Disorder (SUD). WILEY INTERDISCIPLINARY REVIEWS. NANOMEDICINE AND NANOBIOTECHNOLOGY 2025; 17:e70008. [PMID: 40190158 PMCID: PMC11973540 DOI: 10.1002/wnan.70008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/13/2025] [Revised: 02/28/2025] [Accepted: 03/10/2025] [Indexed: 04/09/2025]
Abstract
The field of nanomedicine offers revolutionary potential to reshape the discovery and development of therapeutics for diverse human diseases. However, its application has been limited in improving Substance Use Disorders (SUDs), which represent a profound public health crisis, including major types such as opioid, alcohol, stimulant, and cannabis use disorders. Pharmacotherapy, a cornerstone of SUD management, has reduced morbidity, mortality, and the societal impact of addiction, though its efficacy has ranged from none to moderate. Thus, there is a major unmet need to transform SUD pharmacotherapy to curb the epidemic of addiction. This article explores the potential roles of nanomedicine-inspired precision-targeted drug delivery, sustained release, and combination therapies to increase therapeutic efficacy and minimize side effects. Additionally, it discusses innovative mechanisms that align with the neurobiological complexities of addiction and synergistic approaches that integrate nanomedicine with behavioral interventions, device-based therapies, and emerging modalities such as immunotherapy and neurostimulation. Despite these advancements, barriers such as treatment accessibility, adherence challenges, and inequitable resource distribution persist, particularly in underserved populations. By harnessing the transformative capabilities of nanomedicine and integrating it into holistic, equitable, and personalized care frameworks, this review highlights a path forward to revolutionize the SUD pharmacotherapy landscape. The article underscores the need for continued nano-SUD pharmacotherapy research and the development of strategies to alleviate the substantial burden of addiction on individuals, families, and society.
Collapse
Affiliation(s)
- Akshata Y. Patne
- Center for Research and Education in Nanobioengineering, Department of Internal Medicine, Morsani College of MedicineUniversity of South FloridaTampaFloridaUSA
- Graduate Programs, Taneja College of Pharmacy, MDC30, 12908 USF Health DriveTampaFloridaUSA
| | - Subhra Mohapatra
- Center for Research and Education in Nanobioengineering, Department of Internal Medicine, Morsani College of MedicineUniversity of South FloridaTampaFloridaUSA
- Department of Molecular Medicine, Morsani College of MedicineUniversity of South FloridaTampaFloridaUSA
- Research ServiceJames A. Haley Veterans HospitalTampaFloridaUSA
| | - Shyam S. Mohapatra
- Center for Research and Education in Nanobioengineering, Department of Internal Medicine, Morsani College of MedicineUniversity of South FloridaTampaFloridaUSA
- Graduate Programs, Taneja College of Pharmacy, MDC30, 12908 USF Health DriveTampaFloridaUSA
- Research ServiceJames A. Haley Veterans HospitalTampaFloridaUSA
| |
Collapse
|
|
5
|
Lu TL, Liutkevičienė R, Rovite V, Gao ZH, Wu SN. Evaluation of Small-Molecule Candidates as Modulators of M-Type K + Currents: Impacts on Current Amplitude, Gating, and Voltage-Dependent Hysteresis. Int J Mol Sci 2025; 26:1504. [PMID: 40003973 PMCID: PMC11855363 DOI: 10.3390/ijms26041504] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2024] [Revised: 01/24/2025] [Accepted: 01/29/2025] [Indexed: 02/27/2025] Open
Abstract
The core subunits of the KV7.2, KV7.3, and KV7.5 channels, encoded by the KCNQ2, KCNQ3, and KCNQ5 genes, are expressed across various cell types and play a key role in generating the M-type K+ current (IK(M)). This current is characterized by an activation threshold at low voltages and displays slow activation and deactivation kinetics. Variations in the amplitude and gating kinetics of IK(M) can significantly influence membrane excitability. Notably, IK(M) demonstrates distinct voltage-dependent hysteresis when subjected to prolonged isosceles-triangular ramp pulses. In this review, we explore various small-molecule modulators that can either inhibit or enhance the amplitude of IK(M), along with their perturbations on its gating kinetics and voltage-dependent hysteresis. The inhibitors of IK(M) highlighted here include bisoprolol, brivaracetam, cannabidiol, nalbuphine, phenobarbital, and remdesivir. Conversely, compounds such as flupirtine, kynurenic acid, naringenin, QO-58, and solifenacin have been shown to enhance IK(M). These modulators show potential as pharmacological or therapeutic strategies for treating certain disorders linked to gain-of-function or loss-of-function mutations in M-type K+ (KV7x or KCNQx) channels.
Collapse
Affiliation(s)
- Te-Ling Lu
- Department of Pharmacy, China Medical University, Taichung 406040, Taiwan;
| | - Rasa Liutkevičienė
- Neuroscience Institute, Medical Academy, Lithuanian University of Health Sciences, Eiveniu 2, 50161 Kaunas, Lithuania;
| | - Vita Rovite
- Latvian Biomedical Research and Study Centre (BMC), LV-1067 Riga, Latvia;
| | - Zi-Han Gao
- Institute of Basic Medical Sciences, College of Medical, National Cheng Kung University, Tainan City 701401, Taiwan;
| | - Sheng-Nan Wu
- Institute of Basic Medical Sciences, College of Medical, National Cheng Kung University, Tainan City 701401, Taiwan;
- Department of Research and Education, An Nan Hospital, China Medical University, Tainan City 709204, Taiwan
- School of Medicine, National Sun Yat-sen University, Kaohsiung 804201, Taiwan
| |
Collapse
|
|
6
|
Aparicio-Blanco J, Pucci C, De Pasquale D, Marino A, Debellis D, Ciofani G. Development and characterization of lipid nanocapsules loaded with iron oxide nanoparticles for magnetic targeting to the blood-brain barrier. Drug Deliv Transl Res 2024; 14:3494-3511. [PMID: 38739319 PMCID: PMC11499457 DOI: 10.1007/s13346-024-01587-w] [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] [Accepted: 03/25/2024] [Indexed: 05/14/2024]
Abstract
Brain drug delivery is severely hindered by the presence of the blood-brain barrier (BBB). Its functionality relies on the interactions of the brain endothelial cells with additional cellular constituents, including pericytes, astrocytes, neurons, or microglia. To boost brain drug delivery, nanomedicines have been designed to exploit distinct delivery strategies, including magnetically driven nanocarriers as a form of external physical targeting to the BBB. Herein, a lipid-based magnetic nanocarrier prepared by a low-energy method is first described. Magnetic nanocapsules with a hydrodynamic diameter of 256.7 ± 8.5 nm (polydispersity index: 0.089 ± 0.034) and a ξ-potential of -30.4 ± 0.3 mV were obtained. Transmission electron microscopy-energy dispersive X-ray spectroscopy analysis revealed efficient encapsulation of iron oxide nanoparticles within the oily core of the nanocapsules. Both thermogravimetric analysis and phenanthroline-based colorimetric assay showed that the iron oxide percentage in the final formulation was 12 wt.%, in agreement with vibrating sample magnetometry analysis, as the specific saturation magnetization of the magnetic nanocapsules was 12% that of the bare iron oxide nanoparticles. Magnetic nanocapsules were non-toxic in the range of 50-300 μg/mL over 72 h against both the human cerebral endothelial hCMEC/D3 and Human Brain Vascular Pericytes cell lines. Interestingly, higher uptake of magnetic nanocapsules in both cell types was evidenced in the presence of an external magnetic field than in the absence of it after 24 h. This increase in nanocapsules uptake was also evidenced in pericytes after only 3 h. Altogether, these results highlight the potential for magnetic targeting to the BBB of our formulation.
Collapse
Affiliation(s)
- Juan Aparicio-Blanco
- Department of Pharmaceutics and Food Technology, Faculty of Pharmacy, Complutense University of Madrid, Plaza Ramón y Cajal, 28040, Madrid, Spain.
- Smart Bio- Interfaces, Istituto Italiano di Tecnologia, Viale Rinaldo Piaggio 34, 56025, Pontedera, Italy.
- Institute of Industrial Pharmacy, Complutense University of Madrid, Madrid, Spain.
| | - Carlotta Pucci
- Smart Bio- Interfaces, Istituto Italiano di Tecnologia, Viale Rinaldo Piaggio 34, 56025, Pontedera, Italy
| | - Daniele De Pasquale
- Smart Bio- Interfaces, Istituto Italiano di Tecnologia, Viale Rinaldo Piaggio 34, 56025, Pontedera, Italy
| | - Attilio Marino
- Smart Bio- Interfaces, Istituto Italiano di Tecnologia, Viale Rinaldo Piaggio 34, 56025, Pontedera, Italy
| | - Doriana Debellis
- Electron Microscopy Facility, Istituto Italiano di Tecnologia, Via Morego 30, 16163, Genova, Italy
| | - Gianni Ciofani
- Smart Bio- Interfaces, Istituto Italiano di Tecnologia, Viale Rinaldo Piaggio 34, 56025, Pontedera, Italy.
| |
Collapse
|
|
7
|
Wang J, Zhu X, Jiang H, Ji M, Wu Y, Chen J. Cancer cell-derived exosome based dual-targeted drug delivery system for non-small cell lung cancer therapy. Colloids Surf B Biointerfaces 2024; 244:114141. [PMID: 39216444 DOI: 10.1016/j.colsurfb.2024.114141] [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: 05/13/2024] [Revised: 07/20/2024] [Accepted: 08/04/2024] [Indexed: 09/04/2024]
Abstract
Lung cancer is among most prevalent cancers in the world, in which non-small cell lung cancer (NSCLC) accounts for more than 85 % of all subtypes of lung cancers. NSCLC is often diagnosed at an advanced stage with a high mortality rate. Despite the demonstrated efficacy of chemotherapy in the treatment of NSCLC, the main drawback of current therapy is the lack of an effective drug-targeted delivery system, which may result in undesirable side effects during the clinical treatment. In this study, we construct a "dual-targeting" anti-cancer drug delivery platform by combining superparamagnetic iron oxide nanoparticles (SPIONs) with exosomes derived from NSCLC cells. We successfully promoted the targeted delivery of anti-drug doxorubicin (DOX) at the cellular levels by combining the homing targeted ability of exosomes with the magnetic targeted ability of SPIONs. Moreover, non-small cell lung cancer cell (NCI-h1299) tumor models were established. It was found that exosome-SPIONs (Exo-SPIONs) loaded with DOX exhibited optimal tumor tissue delivery and tumor suppression in the presence of an external magnetic field, and reduced the toxicity of the DOX to normal tissues. The constructed "dual-targeting" anti-cancer drug delivery platform holds promise for targeted chemotherapy for NSCLC.
Collapse
MESH Headings
- Carcinoma, Non-Small-Cell Lung/drug therapy
- Carcinoma, Non-Small-Cell Lung/pathology
- Carcinoma, Non-Small-Cell Lung/metabolism
- Exosomes/chemistry
- Exosomes/metabolism
- Humans
- Lung Neoplasms/drug therapy
- Lung Neoplasms/pathology
- Lung Neoplasms/metabolism
- Doxorubicin/pharmacology
- Doxorubicin/chemistry
- Doxorubicin/administration & dosage
- Drug Delivery Systems
- Animals
- Cell Line, Tumor
- Mice
- Antibiotics, Antineoplastic/pharmacology
- Antibiotics, Antineoplastic/chemistry
- Antibiotics, Antineoplastic/administration & dosage
- Cell Proliferation/drug effects
- Magnetic Iron Oxide Nanoparticles/chemistry
- Cell Survival/drug effects
- Mice, Nude
- Magnetite Nanoparticles/chemistry
- Antineoplastic Agents/pharmacology
- Antineoplastic Agents/chemistry
- Mice, Inbred BALB C
- Drug Screening Assays, Antitumor
Collapse
Affiliation(s)
- Jun Wang
- School of Public Health, Nanjing Medical University, Nanjing 211166, China
| | - Xinyi Zhu
- School of Public Health, Nanjing Medical University, Nanjing 211166, China
| | - Huijun Jiang
- School of Pharmacy, Nanjing Medical University, Nanjing 211166, China
| | - Minghui Ji
- School of Nursing, Nanjing Medical University, Nanjing 211166, China
| | - Yuan Wu
- Department of Medical Oncology, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing 210009, China.
| | - Jin Chen
- School of Public Health, Nanjing Medical University, Nanjing 211166, China; Center for Global Health, The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China; Jiangsu Province Engineering Research Center of Antibody Drug, Key Laboratory of Antibody Technique of National Health Commission, Nanjing Medical University, Nanjing 211166, China.
| |
Collapse
|
|
8
|
Wu T, Zhu W, Duan R, Sun J, Bao S, Chen K, Han B, Chen Y, Lu Y. Magnetic vagus nerve stimulation ameliorates contrast-induced acute kidney injury by circulating plasma exosomal miR-365-3p. J Nanobiotechnology 2024; 22:666. [PMID: 39468562 PMCID: PMC11520859 DOI: 10.1186/s12951-024-02928-0] [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: 02/10/2024] [Accepted: 10/10/2024] [Indexed: 10/30/2024] Open
Abstract
BACKGROUND Contrast-induced acute kidney injury (CI-AKI) is manifested by a rapid decline in renal function occurring within 48-72 h in patients exposed to iodinated contrast media (CM). Although intravenous hydration is currently the effective method confirmed to prevent CI-AKI, it has several drawbacks. Some investigations have demonstrated the nephroprotective effects of vagus nerve stimulation (VNS) against kidney ischemia-reperfusion injury, but no direct research has investigated the use of VNS for treating CI-AKI. Additionally, most current VNS treatment applies invasive electrical stimulator implantation, which is largely limited by the complications. Our recent publications introduce the magnetic vagus nerve stimulation (mVNS) system pioneered and successfully used for the treatment of myocardial infarction. However, it remains uncertain whether mVNS can mitigate CI-AKI and its specific underlying mechanisms. Therefore, we herein evaluate the potential therapeutic effects of mVNS on CM-induced nephropathy in rats and explore the underlying mechanisms. RESULTS mVNS treatment was found to significantly improve the damaged renal function, including the reduction of elevated serum creatinine (Scr), blood urea nitrogen (BUN), and urinary N-acetyl-β-D-glucosaminidase (NAG) with increased urine output. Pathologically, mVNS treatment alleviated the renal tissue structure injury, and suppressed kidney injury molecule-1 (KIM-1) expression and apoptosis in renal tubular epithelial cells. Mechanistically, increased circulating plasma exosomal miR-365-3p after mVNS treatment enhanced the autophagy and reduced CM-induced apoptosis in renal tubular epithelial cells by targeting Ras homolog enriched in brain (Rheb). CONCLUSIONS In summary, we demonstrated that mVNS can improve CI-AKI through enhanced autophagy and apoptosis inhibition, which depended on plasma exosomal miR-365-3p. Our findings highlight the therapeutic potential of mVNS for CI-AKI in clinical practice. However, further research is needed to determine the optimal stimulation parameters to achieve the best therapeutic effects.
Collapse
Affiliation(s)
- Tianyu Wu
- XuZhou Clinical School of Xuzhou Medical University, Department of Central Laboratory, Xuzhou Central Hospital, No.199 Jiefang South Road, Xuzhou, 221009, P.R. China
| | - Wenwu Zhu
- XuZhou Clinical School of Xuzhou Medical University, Department of Cardiology, Xuzhou Central Hospital, XuZhou Institute of Cardiovascular disease, No.199 Jiefang South Road, Xuzhou, 221009, P.R. China
| | - Rui Duan
- XuZhou Clinical School of Xuzhou Medical University, Department of Cardiology, Xuzhou Central Hospital, XuZhou Institute of Cardiovascular disease, No.199 Jiefang South Road, Xuzhou, 221009, P.R. China
| | - Jianfei Sun
- The State Key Laboratory of Bioelectronics, Jiangsu Key Laboratory of Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, Nanjing, 210009, P.R. China
| | - Siyuan Bao
- The State Key Laboratory of Bioelectronics, Jiangsu Key Laboratory of Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, Nanjing, 210009, P.R. China
| | - Kaiyan Chen
- Section of Pacing and Electrophysiology, Division of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Guangzhou Road 300, Nanjing, 210029, P.R. China
| | - Bing Han
- XuZhou Clinical School of Xuzhou Medical University, Department of Cardiology, Xuzhou Central Hospital, XuZhou Institute of Cardiovascular disease, No.199 Jiefang South Road, Xuzhou, 221009, P.R. China.
| | - Yuqiong Chen
- Department of Cardiology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, 215000, PR China.
| | - Yao Lu
- XuZhou Clinical School of Xuzhou Medical University, Department of Cardiology, Xuzhou Central Hospital, XuZhou Institute of Cardiovascular disease, No.199 Jiefang South Road, Xuzhou, 221009, P.R. China.
| |
Collapse
|
|
9
|
Markowska A, Tarnacka B. Molecular Changes in the Ischemic Brain as Non-Invasive Brain Stimulation Targets-TMS and tDCS Mechanisms, Therapeutic Challenges, and Combination Therapies. Biomedicines 2024; 12:1560. [PMID: 39062133 PMCID: PMC11274560 DOI: 10.3390/biomedicines12071560] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2024] [Revised: 07/07/2024] [Accepted: 07/10/2024] [Indexed: 07/28/2024] Open
Abstract
Ischemic stroke is one of the leading causes of death and disability. As the currently used neurorehabilitation methods present several limitations, the ongoing research focuses on the use of non-invasive brain stimulation (NIBS) techniques such as transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS). NIBS methods were demonstrated to modulate neural excitability and improve motor and cognitive functioning in neurodegenerative diseases. However, their mechanisms of action are not fully elucidated, and the clinical outcomes are often unpredictable. This review explores the molecular processes underlying the effects of TMS and tDCS in stroke rehabilitation, including oxidative stress reduction, cell death, stimulation of neurogenesis, and neuroprotective phenotypes of glial cells. A highlight is put on the newly emerging therapeutic targets, such as ferroptotic and pyroptotic pathways. In addition, the issue of interindividual variability is discussed, and the role of neuroimaging techniques is investigated to get closer to personalized medicine. Furthermore, translational challenges of NIBS techniques are analyzed, and limitations of current clinical trials are investigated. The paper concludes with suggestions for further neurorehabilitation stroke treatment, putting the focus on combination and personalized therapies, as well as novel protocols of brain stimulation techniques.
Collapse
Affiliation(s)
- Aleksandra Markowska
- Department of Rehabilitation Medicine, Faculty of Medicine, Warsaw Medical University, Spartańska 1, 02-637 Warsaw, Poland;
| | | |
Collapse
|
|
10
|
Afshari M, Gharibzadeh S, Pouretemad H, Roghani M. Reversing valproic acid-induced autism-like behaviors through a combination of low-frequency repeated transcranial magnetic stimulation and superparamagnetic iron oxide nanoparticles. Sci Rep 2024; 14:8082. [PMID: 38582936 PMCID: PMC10998842 DOI: 10.1038/s41598-024-58871-5] [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: 01/13/2024] [Accepted: 04/03/2024] [Indexed: 04/08/2024] Open
Abstract
Transcranial magnetic stimulation (TMS) is a neurostimulation device used to modulate brain cortex activity. Our objective was to enhance the therapeutic effectiveness of low-frequency repeated TMS (LF-rTMS) in a rat model of autism spectrum disorder (ASD) induced by prenatal valproic acid (VPA) exposure through the injection of superparamagnetic iron oxide nanoparticles (SPIONs). For the induction of ASD, we administered prenatal VPA (600 mg/kg, I.P.) on the 12.5th day of pregnancy. At postnatal day 30, SPIONs were injected directly into the lateral ventricle of the brain. Subsequently, LF-rTMS treatment was applied for 14 consecutive days. Following the treatment period, behavioral analyses were conducted. At postnatal day 60, brain tissue was extracted, and both biochemical and histological analyses were performed. Our data revealed that prenatal VPA exposure led to behavioral alterations, including changes in social interactions, increased anxiety, and repetitive behavior, along with dysfunction in stress coping strategies. Additionally, we observed reduced levels of SYN, MAP2, and BDNF. These changes were accompanied by a decrease in dendritic spine density in the hippocampal CA1 area. However, LF-rTMS treatment combined with SPIONs successfully reversed these dysfunctions at the behavioral, biochemical, and histological levels, introducing a successful approach for the treatment of ASD.
Collapse
Affiliation(s)
- Masoud Afshari
- Department of Cognitive Psychology, Institute for Cognitive and Brain Sciences, Shahid Beheshti University, Tehran, Iran
| | - Shahriar Gharibzadeh
- Department of Cognitive Psychology, Institute for Cognitive and Brain Sciences, Shahid Beheshti University, Tehran, Iran.
| | - Hamidreza Pouretemad
- Department of Cognitive Psychology, Institute for Cognitive and Brain Sciences, Shahid Beheshti University, Tehran, Iran
| | - Mehrdad Roghani
- Neurophysiology Research Center, Shahed University, Tehran, Iran.
| |
Collapse
|
|
11
|
Du W, Wang T, Hu S, Luan J, Tian F, Ma G, Xue J. Engineering of electrospun nanofiber scaffolds for repairing brain injury. ENGINEERED REGENERATION 2023; 4:289-303. [DOI: 10.1016/j.engreg.2023.04.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/14/2023] Open
|
|
12
|
Zhu X, Wang J, Cai L, Wu Y, Ji M, Jiang H, Chen J. Dissection of the antibacterial mechanism of zinc oxide nanoparticles with manipulable nanoscale morphologies. JOURNAL OF HAZARDOUS MATERIALS 2022; 430:128436. [PMID: 35158241 DOI: 10.1016/j.jhazmat.2022.128436] [Citation(s) in RCA: 50] [Impact Index Per Article: 16.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/24/2021] [Revised: 01/27/2022] [Accepted: 02/03/2022] [Indexed: 06/14/2023]
Abstract
Despite the extensive uses of ZnO nanoparticles as promising antimicrobial agents to tackle the severe microbial infections, the systematic antibacterial studies on ZnO nanoparticles with manipulable nanoscale morphologies at the genetic expression level remain ill-defined. In this study, via a controllable thermal decomposition, ZnO nanoparticles of different morphologies were facilely prepared. Additionally, the surface PEGylation of ZnO was conducted to obtain the nanoparticles of low biotoxicity. While all the prepared ZnO nanoparticles exhibited the significantly chemical activities, the pronounced antibacterial effect of obtained ZnO nanoparticles was also identified, in which the ultra-small ones (~5 nm) showed the best performance. Moreover, the antibacterial activities of ZnO nanoparticles were studied by bacterial nucleic acid leakage, alkaline phosphatase, biofilm and reactive oxygen species (ROS) assays. Furthermore, the transcriptome analysis of ZnO nanoparticles with different morphologies against Escherichia coli (E. coli) revealed the underlying antibacterial mechanism involved the signal transduction, material transport, energy metabolism and other biological processes. Therefore, the cost-effective preparation of ZnO nanoparticles with distinct morphological features provides insights for the development of application specific antibacterial agents.
Collapse
Affiliation(s)
- Xinyi Zhu
- Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing 211166, China
| | - Jun Wang
- Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing 211166, China
| | - Ling Cai
- School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189, China
| | - Yuan Wu
- Department of Medical Oncology, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing 210009, China
| | - Minghui Ji
- School of Nursing, Nanjing Medical University, Nanjing 211166, China
| | - Huijun Jiang
- School of Pharmacy, Nanjing Medical University, 211166 Nanjing, China
| | - Jin Chen
- Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing 211166, China; School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189, China; Jiangsu Province Engineering Research Center of Antibody Drug, Key Laboratory of Antibody Technique of National Health Commission, Nanjing Medical University, Nanjing 211166, China; The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, 211166 Nanjing, China.
| |
Collapse
|
|
13
|
Zhang L, Sun H, Zhao J, Lee J, Ee Low L, Gong L, Chen Y, Wang N, Zhu C, Lin P, Liang Z, Wei M, Ling D, Li F. Dynamic nanoassemblies for imaging and therapy of neurological disorders. Adv Drug Deliv Rev 2021; 175:113832. [PMID: 34146626 DOI: 10.1016/j.addr.2021.113832] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2021] [Revised: 05/07/2021] [Accepted: 06/11/2021] [Indexed: 02/07/2023]
Abstract
The past decades have witnessed an increased incidence of neurological disorders (NDs) such as Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, ischemic stroke, and epilepsy, which significantly lower patients' life quality and increase the economic and social burden. Recently, nanomedicines composed of imaging and/or therapeutic agents have been explored to diagnose and/or treat NDs due to their enhanced bioavailability, blood-brain barrier (BBB) permeability, and targeting capacity. Intriguingly, dynamic nanoassemblies self-assembled from functional nanoparticles to simultaneously interfere with multiple pathogenic substances and pathological changes, have been regarded as one of the foremost candidates to improve the diagnostic and therapeutic efficacy of NDs. To help readers better understand this emerging field, in this review, the pathogenic mechanism of different types of NDs is briefly introduced, then the functional nanoparticles used as building blocks in the construction of dynamic nanoassemblies for NDs theranostics are summarized. Furthermore, dynamic nanoassemblies that can actively cross the BBB to target brain lesions, sensitively and efficiently diagnose or treat NDs, and effectively promote neuroregeneration are highlighted. Finally, we conclude with our perspectives on the future development in this field.
Collapse
|
|
14
|
Lu QB, Sun JF, Yang QY, Cai WW, Xia MQ, Wu FF, Gu N, Zhang ZJ. Magnetic brain stimulation using iron oxide nanoparticle-mediated selective treatment of the left prelimbic cortex as a novel strategy to rapidly improve depressive-like symptoms in mice. Zool Res 2020; 41:381-394. [PMID: 32400977 PMCID: PMC7340515 DOI: 10.24272/j.issn.2095-8137.2020.076] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
Magnetic brain stimulation has greatly contributed to the advancement of neuroscience. However, challenges remain in the power of penetration and precision of magnetic stimulation, especially in small animals. Here, a novel combined magnetic stimulation system (c-MSS) was established for brain stimulation in mice. The c-MSS uses a mild magnetic pulse sequence and injection of superparamagnetic iron oxide (SPIO) nanodrugs to elevate local cortical susceptibility. After imaging of the SPIO nanoparticles in the left prelimbic (PrL) cortex in mice, we determined their safety and physical characteristics. Depressive-like behavior was established in mice using a chronic unpredictable mild stress (CUMS) model. SPIO nanodrugs were then delivered precisely to the left PrL cortex using in situ injection. A 0.1 T magnetic field (adjustable frequency) was used for magnetic stimulation (5 min/session, two sessions daily). Biomarkers representing therapeutic effects were measured before and after c-MSS intervention. Results showed that c-MSS rapidly improved depressive-like symptoms in CUMS mice after stimulation with a 10 Hz field for 5 d, combined with increased brain-derived neurotrophic factor (BDNF) and inactivation of hypothalamic-pituitary-adrenal (HPA) axis function, which enhanced neuronal activity due to SPIO nanoparticle-mediated effects. The c-MSS was safe and effective, representing a novel approach in the selective stimulation of arbitrary cortical targets in small animals, playing a bioelectric role in neural circuit regulation, including antidepressant effects in CUMS mice. This expands the potential applications of magnetic stimulation and progresses brain research towards clinical application.
Collapse
Affiliation(s)
- Qing-Bo Lu
- Department of Neurology, Affiliated Zhongda Hospital, School of Medicine, Institution of Neuropsychiatry, Southeast University, Nanjing, Jiangsu 210009, China
| | - Jian-Fei Sun
- State Key Laboratory of Bioelectronics, Jiangsu Key Laboratory of Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, Nanjing, Jiangsu 210009, China. E-mail:
| | - Qu-Yang Yang
- State Key Laboratory of Bioelectronics, Jiangsu Key Laboratory of Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, Nanjing, Jiangsu 210009, China
| | - Wen-Wen Cai
- Department of Neurology, Affiliated Zhongda Hospital, School of Medicine, Institution of Neuropsychiatry, Southeast University, Nanjing, Jiangsu 210009, China
| | - Meng-Qin Xia
- Department of Neurology, Affiliated Zhongda Hospital, School of Medicine, Institution of Neuropsychiatry, Southeast University, Nanjing, Jiangsu 210009, China
| | - Fang-Fang Wu
- Department of Neurology, Affiliated Zhongda Hospital, School of Medicine, Institution of Neuropsychiatry, Southeast University, Nanjing, Jiangsu 210009, China
| | - Ning Gu
- State Key Laboratory of Bioelectronics, Jiangsu Key Laboratory of Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, Nanjing, Jiangsu 210009, China. E-mail:
| | - Zhi-Jun Zhang
- Department of Neurology, Affiliated Zhongda Hospital, School of Medicine, Institution of Neuropsychiatry, Southeast University, Nanjing, Jiangsu 210009, China. E-mail:
| |
Collapse
|
|
15
|
Xu Z, Xu J, Yang W, Lin H, Ruan G. Remote neurostimulation with physical fields at cellular level enabled by nanomaterials: Toward medical applications. APL Bioeng 2020; 4:040901. [PMID: 33195958 PMCID: PMC7647612 DOI: 10.1063/5.0022206] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2020] [Accepted: 10/23/2020] [Indexed: 12/29/2022] Open
Abstract
Most neurological diseases have no cure today; innovations in neurotechnology are in urgent need. Nanomaterial-based remote neurostimulation with physical fields (NNSPs) is an emerging class of neurotechnologies that has generated tremendous interest in recent years. This perspective focuses on the clinical translation of this new class of neurotechnologies, an issue that so far has not received enough attention. We outline the major barriers in their clinical translation. We highlight our recent efforts to tackle these translational barriers, with a focus on the biological delivery problem. In particular, for the first time, we have shown that it is feasible to use noninvasive brain delivery to generate significant physiological responses in living animals by NNSP. However, much more work is needed to overcome the translational barriers.
Collapse
Affiliation(s)
| | | | | | | | - Gang Ruan
- Author to whom correspondence should be addressed:
| |
Collapse
|
|
16
|
Luan D, Zhao MG, Shi YC, Li L, Cao YJ, Feng HX, Zhang ZJ. Mechanisms of repetitive transcranial magnetic stimulation for anti-depression: Evidence from preclinical studies. World J Psychiatry 2020; 10:223-233. [PMID: 33134113 PMCID: PMC7582130 DOI: 10.5498/wjp.v10.i10.223] [Citation(s) in RCA: 10] [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: 06/16/2020] [Revised: 08/11/2020] [Accepted: 09/02/2020] [Indexed: 02/05/2023] Open
Abstract
This review summarizes the anti-depressant mechanisms of repetitive transcranial magnetic stimulation in preclinical studies, including anti-inflammatory effects mediated by activation of nuclear factor-E2-related factor 2 signaling pathway, anti-oxidative stress effects, enhancement of synaptic plasticity and neurogenesis via activation of the endocannabinoid system and brain derived neurotrophic factor signaling pathway, increasing the content of monoamine neurotransmitters via inhibition of Sirtuin 1/monoamine oxidase A signaling pathway, and reducing the activity of the hypothalamic-pituitary-adrenocortical axis. We also discuss the shortcomings of transcranial magnetic stimulation in preclinical studies such as inaccurate positioning, shallow depth of stimulation, and difficulty in elucidating the neural circuit mechanism up- and down-stream of the stimulation target brain region.
Collapse
Affiliation(s)
- Di Luan
- Department of Neurology, Affiliated Zhongda Hospital, Research Institution of Neuropsychiatry, School of Medicine, Southeast University, Nanjing 210009, Jiangsu Province, China
| | - Ming-Ge Zhao
- Department of Nursing, School of Medicine, Southeast University, Nanjing 210009, Jiangsu Province, China
| | - Ya-Chen Shi
- Department of Neurology, Affiliated Zhongda Hospital, Research Institution of Neuropsychiatry, School of Medicine, Southeast University, Nanjing 210009, Jiangsu Province, China
| | - Ling Li
- Department of Neurology, Affiliated Zhongda Hospital, Research Institution of Neuropsychiatry, School of Medicine, Southeast University, Nanjing 210009, Jiangsu Province, China
| | - Yu-Jia Cao
- Department of Neurology, Affiliated Zhongda Hospital, Research Institution of Neuropsychiatry, School of Medicine, Southeast University, Nanjing 210009, Jiangsu Province, China
| | - Hai-Xia Feng
- Department of Nursing, School of Medicine, Southeast University, Nanjing 210009, Jiangsu Province, China
| | - Zhi-Jun Zhang
- Department of Neurology, Affiliated Zhongda Hospital, Research Institution of Neuropsychiatry, School of Medicine, Southeast University, Nanjing 210009, Jiangsu Province, China
- Department of Psychology, Xinxiang Medical University, Xinxiang 453003, Henan Province, China
- Mental Health Center, Zhejiang University School of Medicine, Hangzhou 310013, Zhejiang province, China
| |
Collapse
|