{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T02:46:23Z","timestamp":1773197183461,"version":"3.50.1"},"reference-count":35,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,3,8]],"date-time":"2022-03-08T00:00:00Z","timestamp":1646697600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,3,8]],"date-time":"2022-03-08T00:00:00Z","timestamp":1646697600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Bundesanstalt f\u00fcr Materialforschung und -pr\u00fcfung (BAM)"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Upconversion nanoparticles (UCNPs) have attracted considerable attention owing to their unique photophysical properties. Their utilization in biomedical applications depends on the understanding of their transformations under physiological conditions and their potential toxicity. In this study, NaYF<jats:sub>4<\/jats:sub>:Yb,Er UCNPs, widely used for luminescence and photophysical studies, were modified with a set of four different coordinatively bound surface ligands, i.e., citrate, alendronate (AA), ethylendiamine tetra(methylene phosphonate) (EDTMP), and poly(maleic anhydride-alt-1-octadecene) (PMAO), as well as silica coatings with two different thicknesses. Subsequently, the aging-induced release of fluoride ions in water and cell culture media and their cytotoxic profile to human keratinocytes were assessed in parallel to the cytotoxic evaluation of the ligands, sodium fluoride and the lanthanide ions. The cytotoxicity studies of UCNPs with different surface modifications demonstrated the good biocompatibility of EDTMP-UCNPs and PMAO-UCNPs, which is in line with the low amount of fluoride ions released from these samples. An efficient prevention of UCNP dissolution and release of cytotoxic ions, as well as low cytotoxicity was also observed for UCNPs with a sufficiently thick silica shell. Overall, our results provide new insights into the understanding of the contribution of surface chemistry to the stability, dissolution behavior, and cytotoxicity of UCNPs. Altogether, the results obtained are highly important for future applications of UCNPs in the life sciences and bioimaging studies.<\/jats:p>","DOI":"10.1038\/s41598-022-07630-5","type":"journal-article","created":{"date-parts":[[2022,3,8]],"date-time":"2022-03-08T11:04:59Z","timestamp":1646737499000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":64,"title":["Stability, dissolution, and cytotoxicity of NaYF4-upconversion nanoparticles with different coatings"],"prefix":"10.1038","volume":"12","author":[{"given":"Ver\u00f3nica","family":"Bastos","sequence":"first","affiliation":[]},{"given":"P\u00e1r\u00e1stu","family":"Oskoei","sequence":"additional","affiliation":[]},{"given":"Elina","family":"Andresen","sequence":"additional","affiliation":[]},{"given":"Maysoon I.","family":"Saleh","sequence":"additional","affiliation":[]},{"given":"Bastian","family":"R\u00fchle","sequence":"additional","affiliation":[]},{"given":"Ute","family":"Resch-Genger","sequence":"additional","affiliation":[]},{"given":"Helena","family":"Oliveira","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2022,3,8]]},"reference":[{"key":"7630_CR1","doi-asserted-by":"publisher","first-page":"3373","DOI":"10.1021\/acsnano.8b09270","volume":"13","author":"Y Ao","year":"2019","unstructured":"Ao, Y. et al. An upconversion nanoparticle enables near infrared-optogenetic manipulation of the Caenorhabditis elegans motor circuit. ACS Nano 13, 3373\u20133386 (2019).","journal-title":"ACS Nano"},{"key":"7630_CR2","doi-asserted-by":"publisher","first-page":"756","DOI":"10.3390\/biomedicines9070756","volume":"9","author":"MK Mahata","year":"2021","unstructured":"Mahata, M. K., De, R. & Lee, K. T. Near-infrared-triggered upconverting nanoparticles for biomedicine applications. Biomedicines 9, 756 (2021).","journal-title":"Biomedicines"},{"key":"7630_CR3","doi-asserted-by":"publisher","first-page":"1731","DOI":"10.1016\/j.apt.2019.05.027","volume":"30","author":"M Jafari","year":"2019","unstructured":"Jafari, M. & Rezvanpour, A. Upconversion nano-particles from synthesis to cancer treatment: A review. Adv. Powder Technol. 30, 1731\u20131753 (2019).","journal-title":"Adv. Powder Technol."},{"key":"7630_CR4","doi-asserted-by":"publisher","DOI":"10.1016\/j.micromeso.2020.110049","volume":"297","author":"R Han","year":"2020","unstructured":"Han, R. et al. Fabrication of core\/shell\/shell structure nanoparticle with anticancer drug and dual-photosensitizer co-loading for synergistic chemotherapy and photodynamic therapy. Microporous Mesoporous Mater. 297, 110049 (2020).","journal-title":"Microporous Mesoporous Mater."},{"key":"7630_CR5","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12951-019-0560-5","volume":"18","author":"G Liang","year":"2020","unstructured":"Liang, G. et al. Recent progress in the development of upconversion nanomaterials in bioimaging and disease treatment. J. Nanobiotechnol. 18, 1\u201322 (2020).","journal-title":"J. Nanobiotechnol."},{"key":"7630_CR6","doi-asserted-by":"publisher","DOI":"10.1088\/1361-6528\/ab4f36","volume":"31","author":"H Li","year":"2020","unstructured":"Li, H., Wang, X., Huang, D. & Chen, G. Recent advances of lanthanide-doped upconversion nanoparticles for biological applications. Nanotechnology 31, 072001 (2020).","journal-title":"Nanotechnology"},{"key":"7630_CR7","doi-asserted-by":"publisher","first-page":"5808","DOI":"10.1002\/anie.201005159","volume":"50","author":"M Haase","year":"2011","unstructured":"Haase, M. & Sch\u00e4fer, H. Upconverting nanoparticles. Angew. Chem. Int. Ed. 50, 5808\u20135829 (2011).","journal-title":"Angew. Chem. Int. Ed."},{"key":"7630_CR8","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.aca.2014.04.030","volume":"832","author":"MV DaCosta","year":"2014","unstructured":"DaCosta, M. V., Doughan, S., Han, Y. & Krull, U. J. Lanthanide upconversion nanoparticles and applications in bioassays and bioimaging: A review. Anal. Chim. Acta 832, 1\u201333 (2014).","journal-title":"Anal. Chim. Acta"},{"key":"7630_CR9","doi-asserted-by":"publisher","first-page":"976","DOI":"10.1039\/b809132n","volume":"38","author":"F Wang","year":"2009","unstructured":"Wang, F. & Liu, X. Recent advances in the chemistry of lanthanide-doped upconversion nanocrystals. Chem. Soc. Rev. 38, 976\u2013989 (2009).","journal-title":"Chem. Soc. Rev."},{"key":"7630_CR10","doi-asserted-by":"publisher","first-page":"2414","DOI":"10.3390\/s120302414","volume":"12","author":"J Chen","year":"2012","unstructured":"Chen, J. & Zhao, J. X. Upconversion nanomaterials: Synthesis, mechanism, and applications in sensing. Sensors 12, 2414\u20132435 (2012).","journal-title":"Sensors"},{"key":"7630_CR11","doi-asserted-by":"publisher","first-page":"15904","DOI":"10.1039\/C8NR03892A","volume":"10","author":"O Dukhno","year":"2018","unstructured":"Dukhno, O. et al. Time-dependent luminescence loss for individual upconversion nanoparticles upon dilution in aqueous solution. Nanoscale 10, 15904\u201315910 (2018).","journal-title":"Nanoscale"},{"key":"7630_CR12","doi-asserted-by":"publisher","first-page":"35","DOI":"10.3762\/bjnano.12.3","volume":"12","author":"C Kembuan","year":"2021","unstructured":"Kembuan, C., Oliveira, H. & Graf, C. Effect of different silica coatings on the toxicity of upconversion nanoparticles on RAW 264.7 macrophage cells. Beilstein J. Nanotechnol. 12, 35\u201348 (2021).","journal-title":"Beilstein J. Nanotechnol."},{"key":"7630_CR13","doi-asserted-by":"crossref","first-page":"1801233","DOI":"10.1002\/adhm.201801233","volume":"8","author":"H Oliveira","year":"2019","unstructured":"Oliveira, H. et al. Critical Considerations on the Clinical Translation of Upconversion Nanoparticles (UCNPs): Recommendations from the European Upconversion Network (COST Action CM1403). Adv. Healthc. Mater. 8, 1801233 (2019).","journal-title":"Adv. Healthc. Mater."},{"key":"7630_CR14","doi-asserted-by":"publisher","first-page":"656","DOI":"10.1021\/acs.jpcc.6b09301","volume":"121","author":"S Lahtinen","year":"2016","unstructured":"Lahtinen, S. et al. Disintegration of hexagonal NaYF4:Yb3+, Er3+ upconverting nanoparticles in aqueous media: The role of fluoride in solubility equilibrium. J. Phys. Chem. C 121, 656\u2013665 (2016).","journal-title":"J. Phys. Chem. C"},{"key":"7630_CR15","doi-asserted-by":"publisher","first-page":"8222","DOI":"10.1021\/acs.langmuir.6b02675","volume":"32","author":"D Lisjak","year":"2016","unstructured":"Lisjak, D., Plohl, O., Vidmar, J., Majaron, B. & Ponikvar-Svet, M. Dissolution mechanism of upconverting AYF4:Yb, Tm (A = Na or K) nanoparticles in aqueous media. Langmuir 32, 8222\u20138229 (2016).","journal-title":"Langmuir"},{"key":"7630_CR16","doi-asserted-by":"publisher","first-page":"230","DOI":"10.1067\/moe.2001.111757","volume":"91","author":"C Yc","year":"2001","unstructured":"Yc, C. & My, C. Cytotoxicity of fluoride on human pulp cell cultures in vitro. Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. 91, 230\u2013234 (2001).","journal-title":"Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod."},{"key":"7630_CR17","doi-asserted-by":"publisher","first-page":"27393","DOI":"10.1039\/C5RA00902B","volume":"5","author":"D Lisjak","year":"2015","unstructured":"Lisjak, D., Plohl, O., Ponikvar-Svet, M. & Majaron, B. Dissolution of upconverting fluoride nanoparticles in aqueous suspensions. RSC Adv. 5, 27393\u201327397 (2015).","journal-title":"RSC Adv."},{"key":"7630_CR18","doi-asserted-by":"publisher","first-page":"6975","DOI":"10.1039\/C7DT00529F","volume":"46","author":"O Plohl","year":"2017","unstructured":"Plohl, O. et al. Amphiphilic coatings for the protection of upconverting nanoparticles against dissolution in aqueous media. Dalton Trans. 46, 6975\u20136984 (2017).","journal-title":"Dalton Trans."},{"key":"7630_CR19","doi-asserted-by":"publisher","first-page":"3012","DOI":"10.1021\/acsomega.8b03015","volume":"4","author":"N Estebanez","year":"2019","unstructured":"Estebanez, N., Gonz\u00e1lez-B\u00e9jar, M. & P\u00e9rez-Prieto, J. Polysulfonate cappings on upconversion nanoparticles prevent their disintegration in water and provide superior stability in a highly acidic medium. ACS Omega 4, 3012\u20133019 (2019).","journal-title":"ACS Omega"},{"key":"7630_CR20","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0179471","volume":"12","author":"PMA Salom\u00e3o","year":"2017","unstructured":"Salom\u00e3o, P. M. A. et al. The cytotoxic effect of TiF4 and NaF on fibroblasts is influenced by the experimental model, fluoride concentration and exposure time. PLoS ONE 12, e0179471 (2017).","journal-title":"PLoS ONE"},{"key":"7630_CR21","doi-asserted-by":"publisher","first-page":"320","DOI":"10.1016\/j.jcis.2018.11.094","volume":"538","author":"E Palo","year":"2019","unstructured":"Palo, E., Salom\u00e4ki, M. & Lastusaari, M. Restraining fluoride loss from NaYF4: Yb3+, Er3+ upconverting nanoparticles in aqueous environments using crosslinked poly(acrylic acid)\/poly(allylamine hydrochloride) multilayers. J. Colloid Interface Sci. 538, 320\u2013326 (2019).","journal-title":"J. Colloid Interface Sci."},{"key":"7630_CR22","doi-asserted-by":"publisher","first-page":"7759","DOI":"10.1021\/acs.langmuir.8b00869","volume":"34","author":"E Palo","year":"2018","unstructured":"Palo, E. et al. Effective shielding of NaYF4:Yb3+, Er3+ upconverting nanoparticles in aqueous environments using layer-by-layer assembly. Langmuir 34, 7759\u20137766 (2018).","journal-title":"Langmuir"},{"key":"7630_CR23","doi-asserted-by":"publisher","first-page":"1900235","DOI":"10.1002\/ppsc.201900235","volume":"36","author":"SF Himmelsto\u00df","year":"2019","unstructured":"Himmelsto\u00df, S. F. & Hirsch, T. Long-term colloidal and chemical stability in aqueous media of NaYF4-type upconversion nanoparticles modified by ligand-exchange. Part. Part. Syst. Charact. 36, 1900235 (2019).","journal-title":"Part. Part. Syst. Charact."},{"key":"7630_CR24","doi-asserted-by":"publisher","first-page":"1403","DOI":"10.1039\/C4NR05954A","volume":"7","author":"S Wilhelm","year":"2015","unstructured":"Wilhelm, S. et al. Water dispersible upconverting nanoparticles: effects of surface modification on their luminescence and colloidal stability. Nanoscale 7, 1403\u20131410 (2015).","journal-title":"Nanoscale"},{"key":"7630_CR25","doi-asserted-by":"publisher","first-page":"12589","DOI":"10.1039\/D0NR02931A","volume":"12","author":"E Andresen","year":"2020","unstructured":"Andresen, E., W\u00fcrth, C., Prinz, C., Michaelis, M. & Resch-Genger, U. Time-resolved luminescence spectroscopy for monitoring the stability and dissolution behaviour of upconverting nanocrystals with different surface coatings. Nanoscale 12, 12589\u201312601 (2020).","journal-title":"Nanoscale"},{"key":"7630_CR26","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41598-020-76116-z","volume":"10","author":"MI Saleh","year":"2020","unstructured":"Saleh, M. I. et al. Assessing the protective effects of different surface coatings on NaYF4:Yb3+, Er3+ upconverting nanoparticles in buffer and DMEM. Sci. Rep. 10, 1\u201311 (2020).","journal-title":"Sci. Rep."},{"key":"7630_CR27","doi-asserted-by":"publisher","first-page":"1546","DOI":"10.1007\/s12274-014-0641-6","volume":"8","author":"AE Guller","year":"2015","unstructured":"Guller, A. E. et al. Cytotoxicity and non-specific cellular uptake of bare and surface-modified upconversion nanoparticles in human skin cells. Nano Res. 8, 1546\u20131562 (2015).","journal-title":"Nano Res."},{"key":"7630_CR28","doi-asserted-by":"publisher","first-page":"4283","DOI":"10.1039\/C7NR00092H","volume":"9","author":"C W\u00fcrth","year":"2017","unstructured":"W\u00fcrth, C. et al. Excitation power dependent population pathways and absolute quantum yields of upconversion nanoparticles in different solvents. Nanoscale 9, 4283\u20134294 (2017).","journal-title":"Nanoscale"},{"key":"7630_CR29","doi-asserted-by":"publisher","first-page":"5577","DOI":"10.2147\/IJN.S36111","volume":"7","author":"E Fr\u00f6hlich","year":"2012","unstructured":"Fr\u00f6hlich, E. The role of surface charge in cellular uptake and cytotoxicity of medical nanoparticles. Int. J. Nanomed. 7, 5577\u20135591 (2012).","journal-title":"Int. J. Nanomed."},{"key":"7630_CR30","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1186\/1743-8977-7-25","volume":"7","author":"S Bhattacharjee","year":"2010","unstructured":"Bhattacharjee, S. et al. Role of surface charge and oxidative stress in cytotoxicity of organic monolayer-coated silicon nanoparticles towards macrophage NR8383 cells. Part. Fibre Toxicol. 7, 25 (2010).","journal-title":"Part. Fibre Toxicol."},{"key":"7630_CR31","doi-asserted-by":"publisher","first-page":"5301","DOI":"10.1021\/nn100561e","volume":"4","author":"WK Oh","year":"2010","unstructured":"Oh, W. K. et al. Cellular uptake, cytotoxicity, and innate immune response of silica-Titania hollow nanoparticles based on size and surface functionality. ACS Nano 4, 5301\u20135313 (2010).","journal-title":"ACS Nano"},{"key":"7630_CR32","doi-asserted-by":"publisher","first-page":"897","DOI":"10.1021\/bc049951i","volume":"15","author":"CM Goodman","year":"2004","unstructured":"Goodman, C. M., McCusker, C. D., Yilmaz, T. & Rotello, V. M. Toxicity of gold nanoparticles functionalized with cationic and anionic side chains. Bioconjug. Chem. 15, 897\u2013900 (2004).","journal-title":"Bioconjug. Chem."},{"key":"7630_CR33","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41598-018-35513-1","volume":"8","author":"R Rafique","year":"2018","unstructured":"Rafique, R. et al. Morphological evolution of upconversion nanoparticles and their biomedical signal generation. Sci. Rep. 8, 1\u201311 (2018).","journal-title":"Sci. Rep."},{"key":"7630_CR34","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/j.bioactmat.2018.01.002","volume":"3","author":"C Ma","year":"2018","unstructured":"Ma, C. et al. In vitro cytocompatibility evaluation of poly(octamethylene citrate) monomers toward their use in orthopedic regenerative engineering. Bioact. Mater. 3, 19\u201327 (2018).","journal-title":"Bioact. Mater."},{"key":"7630_CR35","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/j.toxlet.2016.03.005","volume":"249","author":"V Bastos","year":"2016","unstructured":"Bastos, V. et al. The influence of Citrate or PEG coating on silver nanoparticle toxicity to a human keratinocyte cell line. Toxicol. Lett. 249, 29\u201341 (2016).","journal-title":"Toxicol. Lett."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-022-07630-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-022-07630-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-022-07630-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,18]],"date-time":"2023-11-18T14:55:35Z","timestamp":1700319335000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-022-07630-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,8]]},"references-count":35,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["7630"],"URL":"https:\/\/doi.org\/10.1038\/s41598-022-07630-5","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,8]]},"assertion":[{"value":"28 November 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 February 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 March 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"3770"}}