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      Lactic acid modified rare earth-based nanomaterials for enhanced radiation therapy by disturbing the glycolysis

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          Abstract

          Deficient deposition of X-rays and strong capacity of repairing damage DNA of cancer cells limit the effect of radiation therapy (RT). Herein, we synthesize CsLu 2F 7 nanoparticles with lactic acid (LA) ligands (CsLu 2F 7-LA) to overcome these limitations. The high-Z atoms of Lu and Cs can deposit more X-rays for generating enhanced hydroxyl radicals (·OH). Meanwhile, the LA ligand will guide CsLu 2F 7-LA to target monocarboxylic acid transporter (MCT) and impede the transportation of free LA, leading to decreased glycolysis and DNA damage repair. Consequently, the curative effect of RT will be enhanced and the strategy of LA accumulation induced radiosensitization is proved by in vivo and in vitro experiments, which will bring prospects for enhanced RT with nanomedicine.

          Supplementary Information

          The online version contains supplementary material available at 10.1186/s12951-022-01694-1.

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          Understanding the Intersections between Metabolism and Cancer Biology

          Matthew Vander Heiden, Ralph DeBerardinis (2017)
          Transformed cells adapt metabolism to support tumor initiation and progression. Specific metabolic activities can participate directly in the process of transformation or support the biological processes that enable tumor growth. Exploiting cancer metabolism for clinical benefit requires defining the pathways that are limiting for cancer progression and understanding the context specificity of metabolic preferences and liabilities in malignant cells. Progress toward answering these questions is providing new insight into cancer biology and can guide the more effective targeting of metabolism to help patients.
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            The tumour microenvironment after radiotherapy: mechanisms of resistance and recurrence.

            Holly Barker, James T-E H Paget, Aadil A Khan … (2015)
            Radiotherapy plays a central part in curing cancer. For decades, most research on improving treatment outcomes has focused on modulating radiation-induced biological effects on cancer cells. Recently, we have better understood that components within the tumour microenvironment have pivotal roles in determining treatment outcomes. In this Review, we describe vascular, stromal and immunological changes that are induced in the tumour microenvironment by irradiation and discuss how these changes may promote radioresistance and tumour recurrence. We also highlight how this knowledge is guiding the development of new treatment paradigms in which biologically targeted agents will be combined with radiotherapy.
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              Lactate: a metabolic key player in cancer.

              Franziska Hirschhaeuser, Ulrike Sattler, Wolfgang Mueller-Klieser (2011)
              Increased glucose uptake and accumulation of lactate, even under normoxic conditions (i.e., aerobic glycolysis or the Warburg Effect), is a common feature of cancer cells. This phenomenon clearly indicates that lactate is not a surrogate of tumor hypoxia. Tumor lactate can predict for metastases and overall survival of patients, as shown by several studies of different entities. Metastasis of tumors is promoted by lactate-induced secretion of hyaluronan by tumor-associated fibroblasts that create a milieu favorable for migration. Lactate itself has been found to induce the migration of cells and cell clusters. Furthermore, radioresistance has been positively correlated with lactate concentrations, suggesting an antioxidative capacity of lactate. Findings on interactions of tumor metabolites with immune cells indicate a contribution of lactate to the immune escape. Furthermore, lactate bridges the gap between high lactate levels in wound healing, chronic inflammation, and cancer development. Tumor cells ensure sufficient oxygen and nutrient supply for proliferation through lactate-induced secretion of VEGF, resulting in the formation of new vessels. In summary, accumulation of lactate in solid tumors is a pivotal and early event in the development of malignancies. The determination of lactate should enter further clinical trials to confirm its relevance in cancer biology. ©2011 AACR
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                Author and article information

                Contributors
                Han Wang: wanghan2021@sjtu.edu.cn
                Dalong Ni: ndl12353@rjh.com.cn
                Youjia Xu: xuyoujia@suda.edu.cn
                Journal
                Journal ID (nlm-ta): J Nanobiotechnology
                Journal ID (iso-abbrev): J Nanobiotechnology
                Title: Journal of Nanobiotechnology
                Publisher: BioMed Central (London )
                ISSN (Electronic): 1477-3155
                Publication date (Electronic): 19 November 2022
                Publication date PMC-release: 19 November 2022
                Publication date Collection: 2022
                Volume: 20
                Electronic Location Identifier: 490
                Affiliations
                [1 ]GRID grid.452666.5, ISNI 0000 0004 1762 8363, Department of Orthopedics, , The Second Affiliated Hospital of Soochow University, ; Suzhou, 215004 Jiangsu China
                [2 ]GRID grid.459351.f, Department of Orthopedics, , Yancheng Third People’s Hospital, ; Yancheng, 224001 Jiangsu China
                [3 ]GRID grid.16821.3c, ISNI 0000 0004 0368 8293, Department of Orthopaedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital, , Shanghai Jiao Tong University School of Medicine, ; Shanghai, 200025 China
                Article
                Publisher ID: 1694
                DOI: 10.1186/s12951-022-01694-1
                PMC ID: 9675198
                PubMed ID: 36403039
                SO-VID: 770c9536-1521-4c99-8e18-ba2251a3472d
                Copyright © © The Author(s) 2022
                License:

                Open AccessThis 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
                Date received : 30 July 2022
                Date accepted : 30 October 2022
                Funding
                Funded by: National Natural Science Foundation of China
                Award ID: 82102190
                Award ID: 82072474
                Award Recipient :
                Funded by: Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support
                Award ID: 20191805
                Award Recipient :
                Funded by: Foundation of National Facility for Translational Medicine (Shanghai)
                Award ID: TMSK-2021-122
                Award Recipient :
                Funded by: National Key R&D Program of China
                Award ID: 2021YFC2501702
                Award Recipient :
                Categories
                Subject: Research
                Custom metadata
                issue-copyright-statement © The Author(s) 2022

                ScienceOpen disciplines: Biotechnology
                Keywords: nanomedicine,rare earth,radiation therapy,lactic acid,glycolysis
                Data availability:
                ScienceOpen disciplines: Biotechnology
                Keywords: nanomedicine, rare earth, radiation therapy, lactic acid, glycolysis

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