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      Application of nanotechnology in the treatment of glomerulonephritis: current status and future perspectives

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          Abstract

          Glomerulonephritis (GN) is the most common cause of end-stage renal failure worldwide; in most cases, it cannot be cured and can only delay the progression of the disease. At present, the main treatment methods include symptomatic therapy, immunosuppressive therapy, and renal replacement therapy. However, effective treatment of GN is hindered by issues such as steroid resistance, serious side effects, low bioavailability, and lack of precise targeting. With the widespread application of nanoparticles in medical treatment, novel methods have emerged for the treatment of kidney diseases. Targeted transportation of drugs, nucleic acids, and other substances to kidney tissues and even kidney cells through nanodrug delivery systems can reduce the systemic effects and adverse reactions of drugs and improve treatment effectiveness. The high specificity of nanoparticles enables them to bind to ion channels and block or enhance channel gating, thus improving inflammation. This review briefly introduces the characteristics of GN, describes the treatment status of GN, systematically summarizes the research achievements of nanoparticles in the treatment of primary GN, diabetic nephropathy and lupus nephritis, analyzes recent therapeutic developments, and outlines promising research directions, such as gas signaling molecule nanodrug delivery systems and ultrasmall nanoparticles. The current application of nanoparticles in GN is summarized to provide a reference for better treatment of GN in the future.

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          Reactive oxygen species in inflammation and tissue injury.

          Abstract Reactive oxygen species (ROS) are key signaling molecules that play an important role in the progression of inflammatory disorders. An enhanced ROS generation by polymorphonuclear neutrophils (PMNs) at the site of inflammation causes endothelial dysfunction and tissue injury. The vascular endothelium plays an important role in passage of macromolecules and inflammatory cells from the blood to tissue. Under the inflammatory conditions, oxidative stress produced by PMNs leads to the opening of inter-endothelial junctions and promotes the migration of inflammatory cells across the endothelial barrier. The migrated inflammatory cells not only help in the clearance of pathogens and foreign particles but also lead to tissue injury. The current review compiles the past and current research in the area of inflammation with particular emphasis on oxidative stress-mediated signaling mechanisms that are involved in inflammation and tissue injury.
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            Therapeutic siRNA: state of the art

            RNA interference (RNAi) is an ancient biological mechanism used to defend against external invasion. It theoretically can silence any disease-related genes in a sequence-specific manner, making small interfering RNA (siRNA) a promising therapeutic modality. After a two-decade journey from its discovery, two approvals of siRNA therapeutics, ONPATTRO® (patisiran) and GIVLAARI™ (givosiran), have been achieved by Alnylam Pharmaceuticals. Reviewing the long-term pharmaceutical history of human beings, siRNA therapy currently has set up an extraordinary milestone, as it has already changed and will continue to change the treatment and management of human diseases. It can be administered quarterly, even twice-yearly, to achieve therapeutic effects, which is not the case for small molecules and antibodies. The drug development process was extremely hard, aiming to surmount complex obstacles, such as how to efficiently and safely deliver siRNAs to desired tissues and cells and how to enhance the performance of siRNAs with respect to their activity, stability, specificity and potential off-target effects. In this review, the evolution of siRNA chemical modifications and their biomedical performance are comprehensively reviewed. All clinically explored and commercialized siRNA delivery platforms, including the GalNAc (N-acetylgalactosamine)–siRNA conjugate, and their fundamental design principles are thoroughly discussed. The latest progress in siRNA therapeutic development is also summarized. This review provides a comprehensive view and roadmap for general readers working in the field.
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              Delivery materials for siRNA therapeutics.

              RNA interference (RNAi) has broad potential as a therapeutic to reversibly silence any gene. To achieve the clinical potential of RNAi, delivery materials are required to transport short interfering RNA (siRNA) to the site of action in the cells of target tissues. This Review provides an introduction to the biological challenges that siRNA delivery materials aim to overcome, as well as a discussion of the way that the most effective and clinically advanced classes of siRNA delivery systems, including lipid nanoparticles and siRNA conjugates, are designed to surmount these challenges. The systems that we discuss are diverse in their approaches to the delivery problem, and provide valuable insight to guide the design of future siRNA delivery materials.
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                Author and article information

                Contributors
                xianwenwang@ahmu.edu.cn
                Journal
                J Nanobiotechnology
                J Nanobiotechnology
                Journal of Nanobiotechnology
                BioMed Central (London )
                1477-3155
                3 January 2024
                3 January 2024
                2024
                : 22
                : 9
                Affiliations
                [1 ]Department of Pathology, School of Basic Medical Sciences, Anhui Medical University, ( https://ror.org/03xb04968) Hefei, 230032 China
                [2 ]GRID grid.452696.a, ISNI 0000 0004 7533 3408, Department of Pathology, , The Second Affiliated Hospital of Anhui Medical University, ; Hefei, 230601 China
                [3 ]Department of Burns, The First Affiliated Hospital of Anhui Medical University, ( https://ror.org/03t1yn780) Hefei, 230022 People’s Republic of China
                [4 ]Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Soochow University, ( https://ror.org/05t8y2r12) Suzhou, 215123 People’s Republic of China
                [5 ]School of Biomedical Engineering, Research and Engineering Center of Biomedical Materials, Anhui Medical University, ( https://ror.org/03xb04968) Hefei, 230032 China
                Article
                2257
                10.1186/s12951-023-02257-8
                10763010
                5bbc45c2-8a62-4c43-ba33-fcd58c57c22a
                © The Author(s) 2023

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 26 October 2023
                : 7 December 2023
                Funding
                Funded by: National Natural Science Foundation of China
                Award ID: 52202343, 82172858
                Funded by: Anhui Province Natural Science Foundation
                Award ID: 2208085QC81, 1208085MH175
                Funded by: Research Fund of Anhui Institute of Translational Medicine
                Award ID: 2022zhyx-C01
                Award Recipient :
                Funded by: Basic and Clinical Cooperative Research and Promotion Program of Anhui Medical University
                Award ID: 2021xkjT028
                Award Recipient :
                Categories
                Review
                Custom metadata
                © BioMed Central Ltd., part of Springer Nature 2024

                Biotechnology
                nanotechnology,nanocarrier,primary glomerulonephritis,diabetic nephropathy,lupus nephritis,therapy

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