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      Recent progress of iron-based nanomaterials in gene delivery and tumor gene therapy

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          Abstract

          Gene therapy aims to modify or manipulate gene expression and change the biological characteristics of living cells to achieve the purpose of treating diseases. The safe, efficient, and stable expression of exogenous genes in cells is crucial for the success of gene therapy, which is closely related to the vectors used in gene therapy. Currently, gene therapy vectors are mainly divided into two categories: viral vectors and non-viral vectors. Viral vectors are widely used due to the advantages of persistent and stable expression, high transfection efficiency, but they also have certain issues such as infectivity, high immunological rejection, randomness of insertion mutation, carcinogenicity, and limited vector capacity. Non-viral vectors have the advantages of non-infectivity, controllable chemical structure, and unlimited vector capacity, but the transfection efficiency is low. With the rapid development of nanotechnology, the unique physicochemical properties of nanomaterials have attracted increasing attention in the field of drug and gene delivery. Among many nanomaterials, iron-based nanomaterials have attracted much attention due to their superior physicochemical properties, such as Fenton reaction, magnetic resonance imaging, magnetothermal therapy, photothermal therapy, gene delivery, magnetically-assisted drug delivery, cell and tissue targeting, and so on. In this paper, the research progress of iron-based nanomaterials in gene delivery and tumor gene therapy is reviewed, and the future application direction of iron-based nanomaterials is further prospected.

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          Ferroptosis as a p53-mediated activity during tumour suppression.

          Although p53-mediated cell-cycle arrest, senescence and apoptosis serve as critical barriers to cancer development, emerging evidence suggests that the metabolic activities of p53 are also important. Here we show that p53 inhibits cystine uptake and sensitizes cells to ferroptosis, a non-apoptotic form of cell death, by repressing expression of SLC7A11, a key component of the cystine/glutamate antiporter. Notably, p53(3KR), an acetylation-defective mutant that fails to induce cell-cycle arrest, senescence and apoptosis, fully retains the ability to regulate SLC7A11 expression and induce ferroptosis upon reactive oxygen species (ROS)-induced stress. Analysis of mutant mice shows that these non-canonical p53 activities contribute to embryonic development and the lethality associated with loss of Mdm2. Moreover, SLC7A11 is highly expressed in human tumours, and its overexpression inhibits ROS-induced ferroptosis and abrogates p53(3KR)-mediated tumour growth suppression in xenograft models. Our findings uncover a new mode of tumour suppression based on p53 regulation of cystine metabolism, ROS responses and ferroptosis.
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            Non-viral vectors for gene-based therapy.

            Gene-based therapy is the intentional modulation of gene expression in specific cells to treat pathological conditions. This modulation is accomplished by introducing exogenous nucleic acids such as DNA, mRNA, small interfering RNA (siRNA), microRNA (miRNA) or antisense oligonucleotides. Given the large size and the negative charge of these macromolecules, their delivery is typically mediated by carriers or vectors. In this Review, we introduce the biological barriers to gene delivery in vivo and discuss recent advances in material sciences, nanotechnology and nucleic acid chemistry that have yielded promising non-viral delivery systems, some of which are currently undergoing testing in clinical trials. The diversity of these systems highlights the recent progress of gene-based therapy using non-viral approaches.
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              Selenium Drives a Transcriptional Adaptive Program to Block Ferroptosis and Treat Stroke

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                Author and article information

                Contributors
                chming1971@126.com
                wangjun016@163.com
                Journal
                J Nanobiotechnology
                J Nanobiotechnology
                Journal of Nanobiotechnology
                BioMed Central (London )
                1477-3155
                2 June 2024
                2 June 2024
                2024
                : 22
                : 309
                Affiliations
                [1 ]Department of Pharmacy, The Second Affiliated Hospital of Army Medical University, ( https://ror.org/03s8txj32) Chongqing, 400037 China
                [2 ]GRID grid.9227.e, ISNI 0000000119573309, Institute of Biomedicine and Biotechnology, Shenzhen Institute of Advanced Technology, , Chinese Academy of Sciences, ; Shenzhen, Guangdong 518055 China
                [3 ]University of Chinese Academy of Sciences, ( https://ror.org/05qbk4x57) Beijing, 100864 China
                [4 ]GRID grid.416208.9, ISNI 0000 0004 1757 2259, Department of Clinical Laboratory Medicine, , Southwest Hospital, Army Medical University, ; Chongqing, 400038 China
                Article
                2550
                10.1186/s12951-024-02550-0
                11145874
                38825720
                893c3762-5c33-4159-8659-d1955b34c35b
                © The Author(s) 2024

                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
                : 14 March 2024
                : 14 May 2024
                Funding
                Funded by: the National Key R&D Program of China
                Award ID: 2022YFC2603800
                Funded by: National Natural Sciences Foundation of China
                Award ID: 82372105
                Funded by: Natural Science Foundation of Chongqing, China
                Award ID: CSTB2022NSCQ-MSX0205
                Categories
                Review
                Custom metadata
                © BioMed Central Ltd., part of Springer Nature 2024

                Biotechnology
                iron-based nanomaterials,gene delivery,magnetic resonance imaging,gene therapy
                Biotechnology
                iron-based nanomaterials, gene delivery, magnetic resonance imaging, gene therapy

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