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      Engineered exosomes from different sources for cancer-targeted therapy

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          Abstract

          Exosome is a subgroup of extracellular vesicles, which has been serving as an efficient therapeutic tool for various diseases. Engineered exosomes are the sort of exosomes modified with surface decoration and internal therapeutic molecules. After appropriate modification, engineered exosomes are able to deliver antitumor drugs to tumor sites efficiently and precisely with fewer treatment-related adverse effects. However, there still exist many challenges for the clinical translation of engineered exosomes. For instance, what sources and modification strategies could endow exosomes with the most efficient antitumor activity is still poorly understood. Additionally, how to choose appropriately engineered exosomes in different antitumor therapies is another unresolved problem. In this review, we summarized the characteristics of engineered exosomes, especially the spatial and temporal properties. Additionally, we concluded the recent advances in engineered exosomes in the cancer fields, including the sources, isolation technologies, modification strategies, and labeling and imaging methods of engineered exosomes. Furthermore, the applications of engineered exosomes in different antitumor therapies were summarized, such as photodynamic therapy, gene therapy, and immunotherapy. Consequently, the above provides the cancer researchers in this community with the latest ideas on engineered exosome modification and new direction of new drug development, which is prospective to accelerate the clinical translation of engineered exosomes for cancer-targeted therapy.

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          Ferroptosis: an iron-dependent form of nonapoptotic cell death.

          Nonapoptotic forms of cell death may facilitate the selective elimination of some tumor cells or be activated in specific pathological states. The oncogenic RAS-selective lethal small molecule erastin triggers a unique iron-dependent form of nonapoptotic cell death that we term ferroptosis. Ferroptosis is dependent upon intracellular iron, but not other metals, and is morphologically, biochemically, and genetically distinct from apoptosis, necrosis, and autophagy. We identify the small molecule ferrostatin-1 as a potent inhibitor of ferroptosis in cancer cells and glutamate-induced cell death in organotypic rat brain slices, suggesting similarities between these two processes. Indeed, erastin, like glutamate, inhibits cystine uptake by the cystine/glutamate antiporter (system x(c)(-)), creating a void in the antioxidant defenses of the cell and ultimately leading to iron-dependent, oxidative death. Thus, activation of ferroptosis results in the nonapoptotic destruction of certain cancer cells, whereas inhibition of this process may protect organisms from neurodegeneration. Copyright © 2012 Elsevier Inc. All rights reserved.
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            MicroRNA therapeutics: towards a new era for the management of cancer and other diseases

            MicroRNAs (miRNAs) are small non-coding RNAs that can modulate mRNA expression. Insights into the roles of miRNAs in development and disease have led to the development of new therapeutic approaches that are based on miRNA mimics or agents that inhibit their functions (antimiRs), and the first such approaches have entered the clinic. This Review discusses the role of different miRNAs in cancer and other diseases, and provides an overview of current miRNA therapeutics in the clinic.
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              Principles of nanoparticle design for overcoming biological barriers to drug delivery.

              Biological barriers to drug transport prevent successful accumulation of nanotherapeutics specifically at diseased sites, limiting efficacious responses in disease processes ranging from cancer to inflammation. Although substantial research efforts have aimed to incorporate multiple functionalities and moieties within the overall nanoparticle design, many of these strategies fail to adequately address these barriers. Obstacles, such as nonspecific distribution and inadequate accumulation of therapeutics, remain formidable challenges to drug developers. A reimagining of conventional nanoparticles is needed to successfully negotiate these impediments to drug delivery. Site-specific delivery of therapeutics will remain a distant reality unless nanocarrier design takes into account the majority, if not all, of the biological barriers that a particle encounters upon intravenous administration. By successively addressing each of these barriers, innovative design features can be rationally incorporated that will create a new generation of nanotherapeutics, realizing a paradigmatic shift in nanoparticle-based drug delivery.
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                Author and article information

                Contributors
                fccsunzq@zzu.edu.cn
                fccqiaobb@zzu.edu.cn
                czw202112@zzu.edu.cn
                Journal
                Signal Transduct Target Ther
                Signal Transduct Target Ther
                Signal Transduction and Targeted Therapy
                Nature Publishing Group UK (London )
                2095-9907
                2059-3635
                15 March 2023
                15 March 2023
                2023
                : 8
                : 124
                Affiliations
                [1 ]GRID grid.412633.1, ISNI 0000 0004 1799 0733, Department of Hepatobiliary and Pancreatic Surgery, , The First Affiliated Hospital of Zhengzhou University, ; Zhengzhou, Henan 450001 China
                [2 ]GRID grid.412633.1, ISNI 0000 0004 1799 0733, Department of Colorectal Surgery, , The First Affiliated Hospital of Zhengzhou University, ; Zhengzhou, Henan 450001 China
                [3 ]GRID grid.412633.1, ISNI 0000 0004 1799 0733, Henan Institute of Interconnected Intelligent Health Management, , The First Affiliated Hospital of Zhengzhou University, ; Zhengzhou, Henan 450001 China
                [4 ]GRID grid.412633.1, ISNI 0000 0004 1799 0733, Department of Ultrasound, , The First Affiliated Hospital of Zhengzhou University, ; Zhengzhou, Henan 450001 China
                [5 ]GRID grid.414008.9, ISNI 0000 0004 1799 4638, Department of Radiotherapy, , Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, ; Zhengzhou, Henan 450001 China
                Author information
                http://orcid.org/0000-0002-9098-7296
                http://orcid.org/0000-0002-2044-8115
                Article
                1382
                10.1038/s41392-023-01382-y
                10017761
                36922504
                33b160c5-831e-48cd-aa40-208a54b3ab03
                © 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 31 October 2022
                : 31 January 2023
                : 22 February 2023
                Funding
                Funded by: 1. The National Natural Science Foundation of China (82173055, 81972663), 2. The Science Project of Henan Natural Science Foundation (212300410074, 202300410446), 3. The Youth Talent Innovation Team Support Program of Zhengzhou University (32320290), 4. The Provincial and Ministry co-constructed key projects of Henan medical science and technology (SBGJ202102134), 5. Key scientific and technological research projects of Henan Provincial Department of Science and Technology (212102310117), 6. Henan Provincial Health Commission and Ministry of Health Co-construction Project, and Henan Provincial Health and Health Commission Joint Construction Project (LHGJ20200158), 7. Henan Province young and middle-aged health science and technology innovation leading talent project (YXKC2022016), 8. Henan Province Medical Affairs Technology Promotion Project (SYJS2022109).
                Categories
                Review Article
                Custom metadata
                © The Author(s) 2023

                drug development,nanobiotechnology
                drug development, nanobiotechnology

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