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      X-ray-Based Techniques to Study the Nano–Bio Interface

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      ACS Nano
      American Chemical Society
      nano−bio interface, X-ray techniques, synchrotron radiation, imaging, nanoparticles, delivery, degradation, spectroscopy

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          Abstract

          X-ray-based analytics are routinely applied in many fields, including physics, chemistry, materials science, and engineering. The full potential of such techniques in the life sciences and medicine, however, has not yet been fully exploited. We highlight current and upcoming advances in this direction. We describe different X-ray-based methodologies (including those performed at synchrotron light sources and X-ray free-electron lasers) and their potentials for application to investigate the nano–bio interface. The discussion is predominantly guided by asking how such methods could better help to understand and to improve nanoparticle-based drug delivery, though the concepts also apply to nano–bio interactions in general. We discuss current limitations and how they might be overcome, particularly for future use in vivo.

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          Radiation exposure from CT scans in childhood and subsequent risk of leukaemia and brain tumours: a retrospective cohort study

          Summary Background Although CT scans are very useful clinically, potential cancer risks exist from associated ionising radiation, in particular for children who are more radiosensitive than adults. We aimed to assess the excess risk of leukaemia and brain tumours after CT scans in a cohort of children and young adults. Methods In our retrospective cohort study, we included patients without previous cancer diagnoses who were first examined with CT in National Health Service (NHS) centres in England, Wales, or Scotland (Great Britain) between 1985 and 2002, when they were younger than 22 years of age. We obtained data for cancer incidence, mortality, and loss to follow-up from the NHS Central Registry from Jan 1, 1985, to Dec 31, 2008. We estimated absorbed brain and red bone marrow doses per CT scan in mGy and assessed excess incidence of leukaemia and brain tumours cancer with Poisson relative risk models. To avoid inclusion of CT scans related to cancer diagnosis, follow-up for leukaemia began 2 years after the first CT and for brain tumours 5 years after the first CT. Findings During follow-up, 74 of 178 604 patients were diagnosed with leukaemia and 135 of 176 587 patients were diagnosed with brain tumours. We noted a positive association between radiation dose from CT scans and leukaemia (excess relative risk [ERR] per mGy 0·036, 95% CI 0·005–0·120; p=0·0097) and brain tumours (0·023, 0·010–0·049; p<0·0001). Compared with patients who received a dose of less than 5 mGy, the relative risk of leukaemia for patients who received a cumulative dose of at least 30 mGy (mean dose 51·13 mGy) was 3·18 (95% CI 1·46–6·94) and the relative risk of brain cancer for patients who received a cumulative dose of 50–74 mGy (mean dose 60·42 mGy) was 2·82 (1·33–6·03). Interpretation Use of CT scans in children to deliver cumulative doses of about 50 mGy might almost triple the risk of leukaemia and doses of about 60 mGy might triple the risk of brain cancer. Because these cancers are relatively rare, the cumulative absolute risks are small: in the 10 years after the first scan for patients younger than 10 years, one excess case of leukaemia and one excess case of brain tumour per 10 000 head CT scans is estimated to occur. Nevertheless, although clinical benefits should outweigh the small absolute risks, radiation doses from CT scans ought to be kept as low as possible and alternative procedures, which do not involve ionising radiation, should be considered if appropriate. Funding US National Cancer Institute and UK Department of Health.
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            Understanding biophysicochemical interactions at the nano-bio interface.

            Rapid growth in nanotechnology is increasing the likelihood of engineered nanomaterials coming into contact with humans and the environment. Nanoparticles interacting with proteins, membranes, cells, DNA and organelles establish a series of nanoparticle/biological interfaces that depend on colloidal forces as well as dynamic biophysicochemical interactions. These interactions lead to the formation of protein coronas, particle wrapping, intracellular uptake and biocatalytic processes that could have biocompatible or bioadverse outcomes. For their part, the biomolecules may induce phase transformations, free energy releases, restructuring and dissolution at the nanomaterial surface. Probing these various interfaces allows the development of predictive relationships between structure and activity that are determined by nanomaterial properties such as size, shape, surface chemistry, roughness and surface coatings. This knowledge is important from the perspective of safe use of nanomaterials.
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              Doxil®--the first FDA-approved nano-drug: lessons learned.

              Doxil®, the first FDA-approved nano-drug (1995), is based on three unrelated principles: (i) prolonged drug circulation time and avoidance of the RES due to the use of PEGylated nano-liposomes; (ii) high and stable remote loading of doxorubicin driven by a transmembrane ammonium sulfate gradient, which also allows for drug release at the tumor; and (iii) having the liposome lipid bilayer in a "liquid ordered" phase composed of the high-T(m) (53 °C) phosphatidylcholine, and cholesterol. Due to the EPR effect, Doxil is "passively targeted" to tumors and its doxorubicin is released and becomes available to tumor cells by as yet unknown means. This review summarizes historical and scientific perspectives of Doxil development and lessons learned from its development and 20 years of its use. It demonstrates the obligatory need for applying an understanding of the cross talk between physicochemical, nano-technological, and biological principles. However, in spite of the large reward, ~2 years after Doxil-related patents expired, there is still no FDA-approved generic "Doxil" available. Copyright © 2012 Elsevier B.V. All rights reserved.
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                Author and article information

                Journal
                ACS Nano
                ACS Nano
                nn
                ancac3
                ACS Nano
                American Chemical Society
                1936-0851
                1936-086X
                02 March 2021
                23 March 2021
                : 15
                : 3
                : 3754-3807
                Affiliations
                []Center for Cooperative Research in Biomaterials (CIC biomaGUNE), Basque Research and Technology Alliance (BRTA) , Paseo de Miramon 182, 20014 Donostia San Sebastián, Spain
                []Universitat Rovira i Virgili , 43007 Tarragona, Spain
                [§ ]ICREA , Passeig Lluís Companys 23, 08010 Barcelona, Spain
                []Department of Materials Science and Engineering, Stanford University , Stanford, California 94305, United States
                []Mathematics, Informatics, and Natural Sciences (MIN) Faculty, University of Hamburg , 20354 Hamburg, Germany
                []Centre for Ultrafast Imaging, Universität Hamburg , 22761 Hamburg, Germany
                [# ]Department of Chemical Engineering, University of Michigan , Ann Arbor, Michigan 48109, United States
                []Biointerfaces Institute, University of Michigan , Ann Arbor, Michigan 48109, United States
                []ARC Centre of Excellence in Convergent Bio-Nano Science and Technology and the Department of Chemical Engineering, The University of Melbourne , Parkville, Victoria 3010, Australia
                []Deutsches Elektronen-Synchrotron DESY , Notkestraße 85, 22607 Hamburg, Germany
                []National Center for Nanoscience and Technology (NCNST) , 100190 Beijing China
                []The Molecular Foundry and Division of Molecular Biophysics and Integrated Bioimaging, Lawrence Berkeley National Laboratory , Berkeley, California 94720, United States
                []Radiology Department, University of Pennsylvania , Philadelphia, Pennsylvania 19104, United States
                []School of Chemistry and Chemical Engineering, Frontiers Science Center for Transformative Molecules and National Center for Translational Medicine, Shanghai Jiao Tong University , Shanghai 200240, China
                []University College Dublin , D04 V1W8 Dublin, Ireland
                []CAN, Fraunhofer Institut , 20146 Hamburg, Germany
                []Department of Radiotherapy and Radiation Oncology, University Medical Center Hamburg-Eppendorf , 20246 Hamburg, Germany
                []Department of Radiotherapy and Radiation Oncology, University Medical Center Hamburg-Eppendorf , 20246 Hamburg, Germany
                []Section Biomedical Imaging, Department of Radiology and Neuroradiology, University Medical Clinic Schleswig-Holstein and Christian-Albrechts-University Kiel , 24105 Kiel, Germany
                [†† ]Universität Hamburg and Center for Free-Electron Laser Science , Luruper Chaussee 149, 22761 Hamburg, Germany
                [‡‡ ]Karolinska University Hospital, Huddinge, and Karolinska Institutet , 17177 Stockholm, Sweden
                [§§ ]College of Engineering and Applied Sciences, Nanjing University , Nanjing 210093, China
                [∥∥ ]Terasaki Institute for Biomedical Innovation , Los Angeles, California 90049, United States
                [⊥⊥ ]Department of Materials Science and Engineering, University of Michigan , Ann Arbor, Michigan 48109, United States
                [## ]Michigan Institute for Translational Nanotechnology (MITRAN) , Ypsilanti, Michigan 48198, United States
                [∇∇ ]State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences , Beijing 100085 China
                [○○ ]Ikerbasque, Basque Foundation for Science , 48013 Bilbao, Spain
                [◆◆ ]Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN) , Paseo de Miramon 182, 20014 Donostia-San Sebastián, Spain
                [¶¶ ]European XFEL , 22869 Schenefeld, Germany
                [□□ ]Department of Chemistry and Physics, La Trobe Institute for Molecular Science, La Trobe University , Melbourne 3086, Victoria, Australia
                [■■ ]Sektion Physik, Ludwig Maximilians Universität München , 80539 München, Germany
                [●● ]Saha Institute of Nuclear Physics , Kolkata 700064, India
                [☆☆ ]Department of Chemistry, Department of Chemical Engineering, and Materials Research Institute, The Pennsylvania State University , University Park, Pensylvania 16802, United States
                [★★ ]Department of Radiology, German Cancer Research Center (DKFZ) , 69120 Heidelberg, Germany
                [△△ ]Department of Physics, University of Wisconsin-Milwaukee , 3135 N. Maryland Avenue, Milwaukee, Wisconsin 53211, United States
                [▲▲ ]Department of Physics, Indian Institute of Science , Bangalore 560012, India
                [▼▼ ]California NanoSystems Institute, University of California, Los Angeles , Los Angeles, California 90095, United States
                [††† ]Department of Materials Science and Engineering, University of California, Los Angeles , Los Angeles, California 90095, United States
                [‡‡‡ ]Molecular Science and Biomedicine Laboratory (MBL) State Key Laboratory of Chemo/Biosensing and Chemometrics College of Chemistry and Chemical Engineering, Hunan University , Changsha 410082, P.R. China
                [§§§ ]Institute of Molecular Biology of National Academy of Sciences of Republic of Armenia , 7 Hasratyan str., 0014 Yerevan, Armenia
                [⊥⊥⊥ ]CANDLE Synchrotron Research Institute , 31 Acharyan str., 0040 Yerevan, Armenia
                [### ]Department of Chemistry and Biochemistry, University of California, Los Angeles , Los Angeles, California 90095, United States
                [∇∇∇ ]Department of Bioengineering, University of California, Los Angeles , Los Angeles, California 90095, United States
                [○○○ ]Bioimaging Center, Shanghai Synchrotron Radiation Facility, Zhangjiang Laboratory, Shanghai Advanced Research Institute, Chinese Academy of Sciences , Shanghai 201210, China
                [◆◆◆ ]Division of Physical Biology, CAS Key Laboratory of Interfacial Physics and Technology, Shanghai Institute of Applied Physics, Chinese Academy of Sciences , Shanghai 201800, China
                Author notes
                Article
                10.1021/acsnano.0c09563
                7992135
                33650433
                cb07c85d-669b-44b5-9e2e-aca77234d25c
                © 2021 American Chemical Society

                Permits non-commercial access and re-use, provided that author attribution and integrity are maintained; but does not permit creation of adaptations or other derivative works ( https://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 13 November 2020
                : 25 January 2021
                Categories
                Review
                Custom metadata
                nn0c09563
                nn0c09563

                Nanotechnology
                nano−bio interface,x-ray techniques,synchrotron radiation,imaging,nanoparticles,delivery,degradation,spectroscopy

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