eprintid: 57486 rev_number: 1 eprint_status: archive userid: 3883 dir: documents_old/00/05/74/86 datestamp: 2024-02-29 12:56:24 lastmod: 2024-02-29 12:56:24 status_changed: 2024-02-29 12:56:24 type: article metadata_visibility: show contact_email: hlavacek@iach.cz; farka@mail.muni.cz; gorris@mail.muni.cz creators_name: Hlaváček, Antonín creators_name: Farka, Zdeněk creators_name: Mickert, Matthias J. creators_name: Kostiv, Uliana creators_name: Brandmeier, Julian C. creators_name: Horák, Daniel creators_name: Skládal, Petr creators_name: Foret, František creators_name: Gorris, Hans H. creators_orcid: 0000-0003-3358-3858 creators_orcid: 0000-0002-6842-7081 creators_orcid: 0000-0002-1542-5998 creators_orcid: creators_orcid: 0000-0001-8650-0492 creators_orcid: creators_orcid: 0000-0002-3868-5725 creators_orcid: creators_orcid: title: Bioconjugates of photon-upconversion nanoparticles for cancer biomarker detection and imaging ispublished: pub subjects: ddc_2_540 institutions: fak12_02 full_text_status: none keywords: LINKED-IMMUNOSORBENT-ASSAY; UPCONVERTING NANOPARTICLES; SURFACE MODIFICATION; SENSITIVE DETECTION; QUANTUM DOTS; LUMINESCENCE; PROTEINS; STRATEGY; CELLS; SIZE abstract: Gorris et al. present the synthesis, biofunctionalization and purification of lanthanide-doped photon-upconversion nanoparticles and describe their application in both immunoassays for sensitive detection of blood-based biomarkers and bioimaging of cancer cells. The detection of cancer biomarkers in histological samples and blood is of paramount importance for clinical diagnosis. Current methods are limited in terms of sensitivity, hindering early detection of disease. We have overcome the shortcomings of currently available staining and fluorescence labeling methods by taking an integrative approach to establish photon-upconversion nanoparticles (UCNP) as a powerful platform for cancer detection. These nanoparticles are readily synthesized in different sizes to yield efficient and tunable short-wavelength light emission under near-infrared excitation, which eliminates optical background interference of the specimen. Here we present a protocol for the synthesis of UCNPs by high-temperature co-precipitation or seed-mediated growth by thermal decomposition, surface modification by silica or poly(ethylene glycol) that renders the particles resistant to nonspecific binding, and the conjugation of streptavidin or antibodies for biological detection. To detect blood-based biomarkers, we present an upconversion-linked immunosorbent assay for the analog and digital detection of the cancer marker prostate-specific antigen. When applied to immunocytochemistry analysis, UCNPs enable the detection of the breast cancer marker human epidermal growth factor receptor 2 with a signal-to-background ratio 50-fold higher than conventional fluorescent labels. UCNP synthesis takes 4.5 d, the preparation of the antibody-silica-UCNP conjugate takes 3 d, the streptavidin-poly(ethylene glycol)-UCNP conjugate takes 2-3 weeks, upconversion-linked immunosorbent assay takes 2-4 d and immunocytochemistry takes 8-10 h. The procedures can be performed after standard laboratory training in nanomaterials research. date_type: published date_online: 2022 date: 2022 publication: Nature Protocols volume: 17 number: 4 publisher: Nature place_of_pub: BERLIN pagerange: 1028-1072 id_number_name: 10.1038/s41596-021-00670-7 id_number_type: doi refereed: yes created_here: yes issn: 1754-2189 issn: 1750-2799 official_url: http://doi.org/10.1038/s41596-021-00670-7 referencetext: Airy G. 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reprint_address: Hlavacek, A (corresponding author), Czech Acad Sci, Inst Analyt Chem, Brno, Czech Republic.; Farka, Z; Gorris, HH (corresponding author), Masaryk Univ, Dept Biochem, Fac Sci, Brno, Czech Republic.; Farka, Z (corresponding author), Masaryk Univ, CEITEC MU, funder_text: German Research Foundation [DFG: GO 1968/ 7-1, GO 1968/6-1]; Czech Science Foundation [21-03156S, 21-04420S]; Ministry of Education, Youth and Sports of the Czech Republic (MEYS CR) [LTAB19011, LQ1601]; [RVO 68081715]|H.H.G. acknowledges support from the German Research Foundation (DFG: GO 1968/ 7-1 (Heisenberg Program) and GO 1968/6-1). A.H. and F.F. acknowledge institutional support grant RVO 68081715. A.H., Z.F., and P.S. acknowledge grant 21-03156S from the Czech Science Foundation. Z.F. and P.S. acknowledge the support of the Ministry of Education, Youth and Sports of the Czech Republic (MEYS CR) under the projects INTER-ACTION (LTAB19011) and CEITEC 2020 (LQ1601). D.H. acknowledges grant 21-04420S from the Czech Science Foundation. We thank P. Bouchal and P. Bouchalova for providing cell slides, N. Velychkivska for NMR measurements and V. Vykoukal for taking TEM images. pubmed_id: 35181766 doi: 10.1038/s41596-021-00670-7 wok_id: 2023-06-27 publication_abbrev: NAT PROTOC publication_iso: Nat. Protoc. wos_categories: Biochemical Research Methods research_areas: Biochemistry & Molecular Biology cor_ur: other fp7_project: no fp7_type: info:eu-repo/semantics/article citation: Hlaváček, Antonín , Farka, Zdeněk , Mickert, Matthias J. , Kostiv, Uliana, Brandmeier, Julian C. , Horák, Daniel, Skládal, Petr , Foret, František und Gorris, Hans H. (2022) Bioconjugates of photon-upconversion nanoparticles for cancer biomarker detection and imaging. Nature Protocols 17 (4), S. 1028-1072.