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      In-situ synthesis of quantum dots in the nucleus of live cells

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          ABSTRACT

          The cell nucleus is the main site for the storage and replication of genetic material, and the synthesis of substances in the nucleus is rhythmic, regular and strictly regulated by physiological processes. However, whether exogenous substances, such as nanoparticles, can be synthesized in situ in the nucleus of live cells has not been reported. Here, we have achieved in-situ synthesis of CdS x Se 1− x quantum dots (QDs) in the nucleus by regulation of the glutathione (GSH) metabolic pathway. High enrichment of GSH in the nucleus can be accomplished by the addition of GSH with the help of the Bcl-2 protein. Then, high-valence Se is reduced to low-valence Se by glutathione-reductase-catalyzed GSH, and interacts with the Cd precursor formed through Cd and thiol-rich proteins, eventually generating QDs in the nucleus. Our work contributes to a new understanding of the syntheses of substances in the cell nucleus and will pave the way for the development of advanced ‘supercells’.

          Abstract

          This study strategically exploits cellular metabolic pathways to synthesize fluorescent quantum dots within the nucleus of live cells, pioneering the new field of synthetic biology.

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          Most cited references33

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          Oxidative stress, protein damage and repair in bacteria

          Oxidative damage can have a devastating effect on the structure and activity of proteins, leading to cell death. This Review discusses how bacteria repair oxidized proteins and highlights the importance of these repair systems in physiology and virulence.
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            Eukaryotic Ribosome Assembly

            Ribosomes, which synthesize the proteins of a cell, comprise ribosomal RNA and ribosomal proteins, which coassemble hierarchically during a process termed ribosome biogenesis. Historically, biochemical and molecular biology approaches have revealed how preribosomal particles form and mature in consecutive steps, starting in the nucleolus and terminating after nuclear export into the cytoplasm. However, only recently, due to the revolution in cryo–electron microscopy, could pseudoatomic structures of different preribosomal particles be obtained. Together with in vitro maturation assays, these findings shed light on how nascent ribosomes progress stepwise along a dynamic biogenesis pathway. Preribosomes assemble gradually, chaperoned by a myriad of assembly factors and small nucleolar RNAs, before they reach maturity and enter translation. This information will lead to a better understanding of how ribosome synthesis is linked to other cellular pathways in humans and how it can cause diseases, including cancer, if disturbed.
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              Multiple glutathione disulfide removal pathways mediate cytosolic redox homeostasis.

              Glutathione is central to cellular redox chemistry. The majority of glutathione redox research has been based on the chemical analysis of whole-cell extracts, which unavoidably destroy subcellular compartment-specific information. Compartment-specific real-time measurements based on genetically encoded fluorescent probes now suggest that the cytosolic glutathione redox potential is about 100 mV more reducing than previously thought. Using these probes in yeast, we show that even during severe oxidative stress, the cytosolic glutathione disulfide (GSSG) concentration is much more tightly regulated than expected and provides a mechanistic explanation for the discrepancy with conventional measurements. GSSG that is not immediately reduced in the cytosol is rapidly transported into the vacuole by the ABC-C transporter Ycf1. The amount of whole-cell GSSG is entirely dependent on Ycf1 and uninformative about the cytosolic glutathione pool. Applying these insights, we identify Trx2 and Grx2 as efficient backup systems to glutathione reductase for cytosolic GSSG reduction.
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                Author and article information

                Contributors
                Journal
                Natl Sci Rev
                Natl Sci Rev
                nsr
                National Science Review
                Oxford University Press
                2095-5138
                2053-714X
                March 2024
                12 January 2024
                12 January 2024
                : 11
                : 3
                : nwae021
                Affiliations
                State Key Laboratory of Medicinal Chemical Biology, Frontiers Science Centre for New Organic Matter, Tianjin Key Laboratory of Biosensing and Molecular Recognition, Research Centre for Analytical Sciences, College of Chemistry, School of Medicine, and Frontiers Science Centre for Cell Responses, Nankai University , Tianjin 300071, China
                Haihe Laboratory of Sustainable Chemical Transformations , Tianjin 300192, China
                State Key Laboratory of Medicinal Chemical Biology, Frontiers Science Centre for New Organic Matter, Tianjin Key Laboratory of Biosensing and Molecular Recognition, Research Centre for Analytical Sciences, College of Chemistry, School of Medicine, and Frontiers Science Centre for Cell Responses, Nankai University , Tianjin 300071, China
                Haihe Laboratory of Sustainable Chemical Transformations , Tianjin 300192, China
                State Key Laboratory of Medicinal Chemical Biology, Frontiers Science Centre for New Organic Matter, Tianjin Key Laboratory of Biosensing and Molecular Recognition, Research Centre for Analytical Sciences, College of Chemistry, School of Medicine, and Frontiers Science Centre for Cell Responses, Nankai University , Tianjin 300071, China
                Haihe Laboratory of Sustainable Chemical Transformations , Tianjin 300192, China
                State Key Laboratory of Medicinal Chemical Biology, Frontiers Science Centre for New Organic Matter, Tianjin Key Laboratory of Biosensing and Molecular Recognition, Research Centre for Analytical Sciences, College of Chemistry, School of Medicine, and Frontiers Science Centre for Cell Responses, Nankai University , Tianjin 300071, China
                State Key Laboratory of Medicinal Chemical Biology, Frontiers Science Centre for New Organic Matter, Tianjin Key Laboratory of Biosensing and Molecular Recognition, Research Centre for Analytical Sciences, College of Chemistry, School of Medicine, and Frontiers Science Centre for Cell Responses, Nankai University , Tianjin 300071, China
                Haihe Laboratory of Sustainable Chemical Transformations , Tianjin 300192, China
                State Key Laboratory of Medicinal Chemical Biology, Frontiers Science Centre for New Organic Matter, Tianjin Key Laboratory of Biosensing and Molecular Recognition, Research Centre for Analytical Sciences, College of Chemistry, School of Medicine, and Frontiers Science Centre for Cell Responses, Nankai University , Tianjin 300071, China
                Haihe Laboratory of Sustainable Chemical Transformations , Tianjin 300192, China
                State Key Laboratory of Medicinal Chemical Biology, Frontiers Science Centre for New Organic Matter, Tianjin Key Laboratory of Biosensing and Molecular Recognition, Research Centre for Analytical Sciences, College of Chemistry, School of Medicine, and Frontiers Science Centre for Cell Responses, Nankai University , Tianjin 300071, China
                Haihe Laboratory of Sustainable Chemical Transformations , Tianjin 300192, China
                State Key Laboratory of Medicinal Chemical Biology, Frontiers Science Centre for New Organic Matter, Tianjin Key Laboratory of Biosensing and Molecular Recognition, Research Centre for Analytical Sciences, College of Chemistry, School of Medicine, and Frontiers Science Centre for Cell Responses, Nankai University , Tianjin 300071, China
                Haihe Laboratory of Sustainable Chemical Transformations , Tianjin 300192, China
                Author notes
                Corresponding author. E-mail: dwpang@ 123456whu.edu.cn

                Equally contributed to this work.

                Author information
                https://orcid.org/0000-0002-0811-7794
                Article
                nwae021
                10.1093/nsr/nwae021
                10896589
                38410827
                71ed3d50-9588-4565-818a-f98639741605
                © The Author(s) 2024. Published by Oxford University Press on behalf of China Science Publishing & Media Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 13 February 2023
                : 21 December 2023
                : 27 December 2023
                : 26 February 2024
                Page count
                Pages: 11
                Funding
                Funded by: National Natural Science Foundation of China, DOI 10.13039/501100001809;
                Award ID: 22293030
                Award ID: 22293032
                Award ID: 91859123
                Funded by: National Key Research and Development Program of China, DOI 10.13039/501100012166;
                Award ID: 2019YFA0210500
                Funded by: Fundamental Research Funds for the Central Universities of China, DOI 10.13039/501100012226;
                Award ID: 63211023
                Categories
                Research Article
                Chemistry
                Nsr/1
                AcademicSubjects/MED00010
                AcademicSubjects/SCI00010

                glutathione,live cell,nucleus,quantum dot,intracellular synthesis

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