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      Macrophage-Targeting DNA Nanomaterials: A Future Direction of Biological Therapy

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          Abstract

          DNA can be used for precise construction of complex and flexible micro-nanostructures, including DNA origami, frame nucleic acids, and DNA hydrogels. DNA nanomaterials have good biocompatibility and can enter macrophages via scavenger receptor-mediated endocytosis. DNA nanomaterials can be uniquely and flexibly designed to ensure efficient uptake by macrophages, which represents a novel strategy to regulate macrophage function. With the development of nanotechnology, major advances have been made in the design and manufacturing of DNA nanomaterials for clinical therapy. In diseases accompanied by macrophage disturbances including tumor, infectious diseases, arthritis, fibrosis, acute lung injury, and atherosclerosis, DNA nanomaterials received considerable attention as potential treatments. However, we lack sufficient information to guarantee precise targeting of macrophages by DNA nanomaterials, which precludes their therapeutic applications. In this review, we summarize recent studies of macrophage-targeting DNA nanomaterials and discuss the limitations and challenges of this approach with regard to its potential use as a biological therapy.

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          Tumour-associated macrophages as treatment targets in oncology

          Tumour-associated macrophages (TAMs) are key drivers of tumour-promoting inflammation and cancer progression, and are important determinants of responsiveness to a range of therapies. Herein, the authors summarize the roles of TAMs in cancer, and discuss the potential of TAM-targeted therapeutic strategies to complement and synergize with other anticancer treatments.
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            Inflammation and Cancer: Triggers, Mechanisms, and Consequences

            Inflammation predisposes to the development of cancer and promotes all stages of tumorigenesis. Cancer cells as well as surrounding stromal and inflammatory cells engage in well-orchestrated reciprocal interactions to form an inflammatory tumor microenvironment (TME). Cells within the TME are highly plastic, continuously changing their phenotypic and functional characteristics. Here we review the origins of inflammation in tumors, and the mechanisms whereby inflammation drives tumor initiation, growth, progression and metastasis. We discuss how tumor promoting inflammation closely resembles inflammatory processes typically found during development, immunity, maintenance of tissue homeostasis or tissue repair, and illuminate the distinctions between tissue-protective and pro-tumorigenic inflammation, including spatio-temporal considerations. Defining the cornerstone rules of engagement governing molecular and cellular mechanisms of tumor-promoting inflammation will be essential for the further development of anti-cancer therapies. Grivennikov and Greten review the mechanisms underlying the initiation of pro-tumorigenic inflammatory responses, how these evolve throughout the different stages of tumor development and the plasticity of the cells within the tumor microenvironment.
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              Macrophages in Tissue Repair, Regeneration, and Fibrosis.

              Inflammatory monocytes and tissue-resident macrophages are key regulators of tissue repair, regeneration, and fibrosis. After tissue injury, monocytes and macrophages undergo marked phenotypic and functional changes to play critical roles during the initiation, maintenance, and resolution phases of tissue repair. Disturbances in macrophage function can lead to aberrant repair, such that uncontrolled production of inflammatory mediators and growth factors, deficient generation of anti-inflammatory macrophages, or failed communication between macrophages and epithelial cells, endothelial cells, fibroblasts, and stem or tissue progenitor cells all contribute to a state of persistent injury, and this could lead to the development of pathological fibrosis. In this review, we discuss the mechanisms that instruct macrophages to adopt pro-inflammatory, pro-wound-healing, pro-fibrotic, anti-inflammatory, anti-fibrotic, pro-resolving, and tissue-regenerating phenotypes after injury, and we highlight how some of these mechanisms and macrophage activation states could be exploited therapeutically.
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                Author and article information

                Journal
                Int J Nanomedicine
                Int J Nanomedicine
                ijn
                International Journal of Nanomedicine
                Dove
                1176-9114
                1178-2013
                23 April 2024
                2024
                : 19
                : 3641-3655
                Affiliations
                [1 ]Department of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, People’s Republic of China
                Author notes
                Correspondence: Li-Jun Yao, Email ljyao@hust.edu.cn
                [*]

                These authors contributed equally to this work

                Author information
                http://orcid.org/0000-0002-7734-881X
                Article
                459288
                10.2147/IJN.S459288
                11055528
                38681094
                e0e7822e-21df-47c4-987c-9fd97e671313
                © 2024 Tu et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                : 12 January 2024
                : 28 March 2024
                Page count
                Figures: 5, Tables: 2, References: 91, Pages: 15
                Funding
                Funded by: the National Natural Science Foundation of China;
                This research was supported by the National Natural Science Foundation of China (NO.81570657, No. 81974102).
                Categories
                Review

                Molecular medicine
                macrophages,dna nanomaterials,therapy,macrophage-related diseases
                Molecular medicine
                macrophages, dna nanomaterials, therapy, macrophage-related diseases

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