{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T11:13:59Z","timestamp":1788779639910,"version":"build-2803163510"},"reference-count":73,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T00:00:00Z","timestamp":1786060800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T00:00:00Z","timestamp":1786060800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"University of Padjadjaran"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Folic acid (FA)-modified gadolinium nanoparticles are promising candidates for magnetic resonance imaging (MRI) contrast agents due to their high cancer specificity. Therefore, this study aims to modify nanoparticles with polyethylene glycol (PEG)-FA to enhance their biocompatibility and specificity toward cervical cancer target via folate receptor (FR)-mediated endocytosis. Spherical nanoparticles less than 20\u00a0nm were characterized by dynamic light scattering and transmission electron microscopy, with UV absorbance peaks at 282 and 362\u00a0nm confirming the successful attachment of FA. Additionally, the zeta potential at \u2212\u200951.23\u00a0mV indicated good colloidal stability. Subsequently, an in vitro investigation was performed using three different FA-expressing cancer cell lines: HEK-293 (\u2212), HeLa (\u2009+), and KB (+\u2009+), demonstrating that the cancer cells remained\u2009&gt;\u200990% viable after 24\u00a0h incubation with the nanoparticles. There was enhanced FA-nanoparticle uptake in HeLa and KB, with minimal uptake in HEK-293 cells. In addition, FA pretreatment reduced uptake, confirming the receptor specificity. Compared to nanoparticles without modification, modified nanoparticles showed a significant increase in uptake in cancer cells expressing the FA receptor (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.0001). These results support the potential of FA-modified gadolinium nanoparticles as a receptor-targeted contrast agent for further cervical cancer MR imaging applications.\n                  <\/jats:p>","DOI":"10.1038\/s41598-026-38700-7","type":"journal-article","created":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T07:36:57Z","timestamp":1786088217000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Exploring the in-vitro evaluation of folic acid-modified gadolinium nanoparticles in HEK-293, HeLa, and KB cancer cells for targeted-MR-imaging agent candidate"],"prefix":"10.1038","volume":"16","author":[{"given":"Retna Putri","family":"Fauzia","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Azmi Aulia","family":"Rahmani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riezki","family":"Amalia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ratna Dini","family":"Haryuni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irkham","family":"Irkham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Husein H.","family":"Bahti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Santhy","family":"Wyantuti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,8,7]]},"reference":[{"key":"38700_CR1","unstructured":"World Health Organization. Cancer. https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/cancer. (2024)."},{"key":"38700_CR2","unstructured":"International Agency for Research on Cancer. Global Cancer Observatory: Cancer Today. https:\/\/gco.iarc.fr\/today\/en\/data-sources-methods#mortality. (2022)."},{"key":"38700_CR3","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/biom10121651","volume":"10","author":"AJ Marko","year":"2020","unstructured":"Marko, A. J. et al. Targeted nanoparticles for fluorescence imaging of folate receptor positive tumors. Biomolecules 10, 1\u201312 (2020).","journal-title":"Biomolecules"},{"key":"38700_CR4","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1038\/s43586-023-00211-4","volume":"3","author":"JC Hsu","year":"2023","unstructured":"Hsu, J. C. et al. Nanomaterial-based contrast agents. Nat. Rev. Methods Prim. 3, 30 (2023).","journal-title":"Nat. Rev. Methods Prim."},{"key":"38700_CR5","doi-asserted-by":"publisher","first-page":"9330","DOI":"10.48048\/tis.2025.9330","volume":"22","author":"RP Fauzia","year":"2025","unstructured":"Fauzia, R. P. et al. Effect of size, charge, and surface functionalization of gadolinium nanoparticles on biocompatibility and cellular uptake as magnetic resonance imaging contrast agents. Trends Sci. 22, 9330\u20139330 (2025).","journal-title":"Trends Sci."},{"key":"38700_CR6","doi-asserted-by":"publisher","first-page":"1890","DOI":"10.3390\/pharmaceutics13111890","volume":"13","author":"MY Ahmad","year":"2021","unstructured":"Ahmad, M. Y. et al. Functionalized lanthanide oxide nanoparticles for tumor targeting, medical imaging, and therapy. Pharmaceutics 13, 1890 (2021).","journal-title":"Pharmaceutics"},{"key":"38700_CR7","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1166\/jbns.2015.1325","volume":"9","author":"T Gayathri","year":"2015","unstructured":"Gayathri, T., Sundaram, N. M. & Kumar, R. A. Gadolinium oxide nanoparticles for Magnetic Resonance Imaging and cancer theranostics. J. Bionanosci. 9, 409\u2013423 (2015).","journal-title":"J. Bionanosci."},{"key":"38700_CR8","doi-asserted-by":"publisher","first-page":"741383","DOI":"10.3389\/fonc.2021.741383","volume":"11","author":"T Zhang","year":"2021","unstructured":"Zhang, T. et al. Facile synthesis of holmium-based nanoparticles as a CT and MRI dual-modal imaging for cancer diagnosis. Front Oncol 11, 741383 (2021).","journal-title":"Front Oncol"},{"key":"38700_CR9","doi-asserted-by":"publisher","first-page":"426","DOI":"10.3390\/diagnostics12020426","volume":"12","author":"S Katal","year":"2022","unstructured":"Katal, S., Eibschutz, L. S., Saboury, B., Gholamrezanezhad, A. & Alavi, A. Advantages and applications of total-body PET scanning. Diagnostics 12, 426 (2022).","journal-title":"Diagnostics"},{"key":"38700_CR10","doi-asserted-by":"publisher","first-page":"06TR01","DOI":"10.1088\/1361-6560\/ab04de","volume":"64","author":"J Wu","year":"2019","unstructured":"Wu, J. & Liu, C. Recent advances in cardiac SPECT instrumentation and imaging methods. Phys. Med. Biol. 64, 06TR01 (2019).","journal-title":"Phys. Med. Biol."},{"key":"38700_CR11","doi-asserted-by":"publisher","first-page":"100226","DOI":"10.1016\/j.onano.2024.100226","volume":"21","author":"AA Rahmani","year":"2025","unstructured":"Rahmani, A. A., Jia, Q., Bahti, H. H., Fauzia, R. P. & Wyantuti, S. Recent advances in lanthanide-based nanoparticle contrast agents for magnetic resonance imaging: Synthesis, characterization, and applications. OpenNano 21, 100226 (2025).","journal-title":"OpenNano"},{"issue":"4","key":"38700_CR12","doi-asserted-by":"publisher","first-page":"129","DOI":"10.3390\/inorganics6040129","volume":"6","author":"S Lacerda","year":"2018","unstructured":"Lacerda, S. Targeted contrast agents for molecular MRI. Inorganics 6(4), 129 (2018).","journal-title":"Inorganics"},{"key":"38700_CR13","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1016\/j.jmmm.2015.11.075","volume":"403","author":"B Babi\u0107-Stoji\u0107","year":"2016","unstructured":"Babi\u0107-Stoji\u0107, B. et al. Gd2O3 nanoparticles stabilized by hydrothermally modified dextrose for positive contrast magnetic resonance imaging. J. Magn. Magn. Mater 403, 118\u2013126 (2016).","journal-title":"J. Magn. Magn. Mater"},{"key":"38700_CR14","doi-asserted-by":"publisher","first-page":"1184","DOI":"10.1002\/jbm.a.35995","volume":"105","author":"MA Chowdhury","year":"2017","unstructured":"Chowdhury, M. A. Metal-organic-frameworks for biomedical applications in drug delivery, and as MRI contrast agents. J. Biomed. Mater. Res. Part A 105, 1184\u20131194 (2017).","journal-title":"J. Biomed. Mater. Res. Part A"},{"key":"38700_CR15","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1080\/1061186X.2019.1703188","volume":"28","author":"T Mortezazadeh","year":"2020","unstructured":"Mortezazadeh, T. et al. In vitro and in vivo characteristics of doxorubicin-loaded cyclodextrine-based polyester modified gadolinium oxide nanoparticles: a versatile targeted theranostic system for tumour chemotherapy and molecular resonance imaging. J. Drug Target 28, 533\u2013546 (2020).","journal-title":"J. Drug Target"},{"key":"38700_CR16","doi-asserted-by":"publisher","first-page":"487","DOI":"10.1007\/s10334-019-00738-2","volume":"32","author":"T Mortezazadeh","year":"2019","unstructured":"Mortezazadeh, T. et al. Gadolinium (III) oxide nanoparticles coated with folic acid-functionalized poly(\u03b2-cyclodextrin-co-pentetic acid) as a biocompatible targeted nano-contrast agent for cancer diagnostic: in vitro and in vivo studies. Magn. Reson. Mater. Phys., Biol. Med. 32, 487\u2013500 (2019).","journal-title":"Magn. Reson. Mater. Phys., Biol. Med."},{"key":"38700_CR17","doi-asserted-by":"publisher","first-page":"129446","DOI":"10.1016\/j.matchemphys.2024.129446","volume":"321","author":"FA Hussein","year":"2024","unstructured":"Hussein, F. A., Joe, I. H. & Al-Musawi, S. Investigation of dextran-coated magnetic nanoparticles encapsulated by medication and modified with folate for targeted drug delivery: Invitro and docking studies. Mater. Chem. Phys. 321, 129446 (2024).","journal-title":"Mater. Chem. Phys."},{"issue":"10","key":"38700_CR18","doi-asserted-by":"publisher","first-page":"6299","DOI":"10.1021\/acsbiomaterials.4c01039","volume":"10","author":"AHF Alnasraui","year":"2024","unstructured":"Alnasraui, A. H. F., Joe, I. H. & Al-Musawi, S. Investigation of folate-functionalized magnetic-gold nanoparticles based targeted drug delivery for liver: In vitro in vivo and docking studies. ACS Biomater. Sci. Eng. 10(10), 6299\u20136313 (2024).","journal-title":"ACS Biomater. Sci. Eng."},{"issue":"1","key":"38700_CR19","doi-asserted-by":"publisher","first-page":"11","DOI":"10.3390\/sci4010011","volume":"4","author":"M Difonzo","year":"2022","unstructured":"Difonzo, M., Fliedel, L., Mignet, N., Andrieux, K. & Alhareth, K. How could nanomedicine improve the safety of contrast agents for mri during pregnancy?. Science 4(1), 11 (2022).","journal-title":"Science"},{"issue":"1","key":"38700_CR20","doi-asserted-by":"publisher","first-page":"11","DOI":"10.3390\/magnetochemistry6010011","volume":"6","author":"N Kostev\u0161ek","year":"2020","unstructured":"Kostev\u0161ek, N. A review on the optimal design of magnetic nanoparticle-based T 2 MRI contrast agents. Magnetochemistry 6(1), 11 (2020).","journal-title":"Magnetochemistry"},{"key":"38700_CR21","doi-asserted-by":"publisher","first-page":"1906539","DOI":"10.1002\/adma.201906539","volume":"33","author":"M Jeon","year":"2021","unstructured":"Jeon, M., Halbert, M. V., Stephen, Z. R. & Zhang, M. Iron oxide nanoparticles as T1 contrast agents for magnetic resonance imaging: fundamentals, challenges, applications, and prospectives. Adv. Mater. 33, 1906539 (2021).","journal-title":"Adv. Mater."},{"issue":"2","key":"38700_CR22","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1007\/s11051-021-05156-x","volume":"23","author":"M Salehipour","year":"2021","unstructured":"Salehipour, M. et al. Recent advances in polymer-coated iron oxide nanoparticles as magnetic resonance imaging contrast agents. J. Nanoparticle Res. 23(2), 48 (2021).","journal-title":"J. Nanoparticle Res."},{"key":"38700_CR23","doi-asserted-by":"publisher","first-page":"175647","DOI":"10.1016\/j.jallcom.2024.175647","volume":"1003","author":"E G\u00f3mez-Gonz\u00e1lez","year":"2024","unstructured":"G\u00f3mez-Gonz\u00e1lez, E. et al. Lanthanide vanadate-based nanoparticles as multimodal T1\u2013T2 MRI contrast agent and NIR luminescent imaging probe. J. Alloys Compounds 1003, 175647 (2024).","journal-title":"J. Alloys Compounds"},{"key":"38700_CR24","doi-asserted-by":"publisher","first-page":"310","DOI":"10.1016\/j.jcis.2022.08.130","volume":"629","author":"E G\u00f3mez-Gonz\u00e1lez","year":"2023","unstructured":"G\u00f3mez-Gonz\u00e1lez, E., N\u00fa\u00f1ez, N. O., Caro, C., Garcia-Mart\u00edn, M. L. & Oca\u00f1a, M. Carboxylate functionalized NaDy(MoO4)2 nanoparticles with tunable size and shape as high magnetic field MRI contrast agents. J Colloid Interface Sci 629, 310\u2013321 (2023).","journal-title":"J Colloid Interface Sci"},{"key":"38700_CR25","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1016\/j.jcis.2020.11.119","volume":"587","author":"E G\u00f3mez-Gonz\u00e1lez","year":"2021","unstructured":"G\u00f3mez-Gonz\u00e1lez, E. et al. Holmium phosphate nanoparticles as negative contrast agents for high-field magnetic resonance imaging: Synthesis, magnetic relaxivity study and in vivo evaluation. J Colloid Interface Sci 587, 131\u2013140 (2021).","journal-title":"J Colloid Interface Sci"},{"key":"38700_CR26","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/nano10091675","volume":"10","author":"MJ Akhtar","year":"2020","unstructured":"Akhtar, M. J., Ahamed, M. & Alhadlaq, H. Gadolinium oxide nanoparticles induce toxicity in human endothelial huvecs via lipid peroxidation, mitochondrial dysfunction and autophagy modulation. Nanomaterials 10, 1\u201318 (2020).","journal-title":"Nanomaterials"},{"issue":"7","key":"38700_CR27","doi-asserted-by":"publisher","first-page":"1458","DOI":"10.3390\/pharmaceutics14071458","volume":"14","author":"SL Ho","year":"2022","unstructured":"Ho, S. L. et al. Mono and multiple tumor-targeting ligand-coated ultrasmall gadolinium oxide nanoparticles: enhanced tumor imaging and blood circulation. Pharmaceutics 14(7), 1458 (2022).","journal-title":"Pharmaceutics"},{"key":"38700_CR28","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1016\/j.apsusc.2017.11.225","volume":"477","author":"X Miao","year":"2019","unstructured":"Miao, X. et al. Ultrasmall Gd2O3 nanoparticles surface-coated by polyacrylic acid (PAA) and their PAA-size dependent relaxometric properties. Appl. Surf. Sci. 477, 111\u2013115 (2019).","journal-title":"Appl. Surf. Sci."},{"issue":"1","key":"38700_CR29","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1186\/s11671-020-03318-9","volume":"15","author":"C Wu","year":"2020","unstructured":"Wu, C. et al. Hyaluronic acid-functionalized gadolinium oxide nanoparticles for magnetic resonance imaging-guided radiotherapy of tumors. Nanoscale Res. Lett. 15(1), 94 (2020).","journal-title":"Nanoscale Res. Lett."},{"key":"38700_CR30","doi-asserted-by":"publisher","first-page":"2","DOI":"10.3390\/diagnostics11010002","volume":"11","author":"YJ Jang","year":"2021","unstructured":"Jang, Y. J. et al. Hydrophilic biocompatible poly(Acrylic acid-co-maleic acid) polymer as a surface-coating ligand of ultrasmall Gd2O3 nanoparticles to obtain a high R1 value and T1 Mr images. Diagnostics 11, 2 (2021).","journal-title":"Diagnostics"},{"issue":"2","key":"38700_CR31","doi-asserted-by":"publisher","first-page":"471","DOI":"10.1148\/radiol.2017162740","volume":"286","author":"AH Behzadi","year":"2018","unstructured":"Behzadi, A. H., Zhao, Y., Farooq, Z. & Prince, M. R. Immediate allergic reactions to gadolinium-based contrast agents: A systematic review and meta-analysis. Radiology 286(2), 471\u2013482 (2018).","journal-title":"Radiology"},{"key":"38700_CR32","doi-asserted-by":"publisher","first-page":"1394","DOI":"10.1016\/j.mri.2016.09.005","volume":"34","author":"J Ramalho","year":"2016","unstructured":"Ramalho, J., Ramalho, M., Jay, M., Burke, L. M. & Semelka, R. C. Gadolinium toxicity and treatment. Magn. Reson. Imaging 34, 1394\u20131398 (2016).","journal-title":"Magn. Reson. Imaging"},{"key":"38700_CR33","doi-asserted-by":"publisher","first-page":"799","DOI":"10.1039\/C8NR07769J","volume":"11","author":"X Han","year":"2019","unstructured":"Han, X., Xu, K., Taratula, O. & Farsad, K. Applications of nanoparticles in biomedical imaging. Nanoscale 11, 799\u2013819 (2019).","journal-title":"Nanoscale"},{"key":"38700_CR34","doi-asserted-by":"publisher","first-page":"829","DOI":"10.1002\/bkcs.12074","volume":"41","author":"S Marasini","year":"2020","unstructured":"Marasini, S. et al. A novel paramagnetic nanoparticle T2 magnetic resonance imaging contrast agent with high colloidal stability: polyacrylic acid-coated ultrafine dysprosium oxide nanoparticles. Bull. Korean Chem. Soc. 41, 829\u2013836 (2020).","journal-title":"Bull. Korean Chem. Soc."},{"key":"38700_CR35","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/ph13100312","volume":"13","author":"H Yue","year":"2020","unstructured":"Yue, H. et al. New class of efficient t2 magnetic resonance imaging contrast agent: Carbon-coated paramagnetic dysprosium oxide nanoparticles. Pharmaceuticals 13, 1\u201317 (2020).","journal-title":"Pharmaceuticals"},{"key":"38700_CR36","first-page":"12010","volume":"2193","author":"H Setiawan","year":"2022","unstructured":"Setiawan, H. et al. Synthesis and characterization of gadolinium nanoparticles using polyol method as a candidate for MRI contrast agent. J. Phys. 2193, 12010 (2022).","journal-title":"J. Phys."},{"key":"38700_CR37","doi-asserted-by":"publisher","first-page":"5381","DOI":"10.1039\/C9CS00309F","volume":"48","author":"JK Tee","year":"2019","unstructured":"Tee, J. K. et al. Nanoparticles\u2019 interactions with vasculature in diseases. Chem. Soc. Rev. 48, 5381\u20135407 (2019).","journal-title":"Chem. Soc. Rev."},{"key":"38700_CR38","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1016\/j.apsusc.2017.01.274","volume":"404","author":"N Babayevska","year":"2017","unstructured":"Babayevska, N. et al. Functionalized multimodal ZnO@ Gd2O3 nanosystems to use as perspective contrast agent for MRI. Appl. Surf. Sci. 404, 129\u2013137 (2017).","journal-title":"Appl. Surf. Sci."},{"key":"38700_CR39","doi-asserted-by":"publisher","first-page":"6387","DOI":"10.2147\/IJN.S210992","volume":"14","author":"K Bola\u00f1os","year":"2019","unstructured":"Bola\u00f1os, K., Kogan, M. J. & Araya, E. Capping gold nanoparticles with albumin to improve their biomedical properties. Int. J. Nanomed. 14, 6387\u20136406 (2019).","journal-title":"Int. J. Nanomed."},{"issue":"9","key":"38700_CR40","doi-asserted-by":"publisher","first-page":"2449","DOI":"10.3390\/nano11092449","volume":"11","author":"A Fatima","year":"2021","unstructured":"Fatima, A. et al. Recent advances in gadolinium based contrast agents for bioimaging applications. Nanomaterials 11(9), 2449 (2021).","journal-title":"Nanomaterials"},{"issue":"1","key":"38700_CR41","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1186\/s12645-022-00145-8","volume":"13","author":"L Smith","year":"2022","unstructured":"Smith, L., Byrne, H. L., Waddington, D. & Kuncic, Z. Nanoparticles for MRI-guided radiation therapy: A review. Cancer Nanotechnol. 13(1), 38 (2022).","journal-title":"Cancer Nanotechnol."},{"key":"38700_CR42","doi-asserted-by":"publisher","first-page":"113721","DOI":"10.1016\/j.colsurfb.2023.113721","volume":"234","author":"J Du","year":"2024","unstructured":"Du, J. et al. Folic acid functionalized gadolinium-doped carbon dots as fluorescence \/ magnetic resonance imaging contrast agent for targeted imaging of liver cancer. Colloids Surf. B Biointerfaces 234, 113721 (2024).","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"38700_CR43","doi-asserted-by":"publisher","first-page":"104988","DOI":"10.1016\/j.mtcomm.2022.104988","volume":"33","author":"Y Zhao","year":"2022","unstructured":"Zhao, Y., Cui, C., Zhan, J. & Xuan, G. Study of folate receptor-targeted macromolecular gadolinium complex tumor contrast agent. Mater. Today Commun. 33, 104988 (2022).","journal-title":"Mater. Today Commun."},{"issue":"9","key":"38700_CR44","doi-asserted-by":"publisher","first-page":"1275","DOI":"10.3390\/biomedicines9091275","volume":"9","author":"E Bellotti","year":"2021","unstructured":"Bellotti, E. et al. Targeting cancer cells overexpressing folate receptors with new terpolymer-based nanocapsules: Toward a novel targeted dna delivery system for cancer therapy. Biomedicines 9(9), 1275 (2021).","journal-title":"Biomedicines"},{"key":"38700_CR45","doi-asserted-by":"publisher","first-page":"122064","DOI":"10.1016\/j.ijpharm.2022.122064","volume":"625","author":"C Movileanu","year":"2022","unstructured":"Movileanu, C. et al. Folic acid-decorated PEGylated magnetite nanoparticles as efficient drug carriers to tumor cells overexpressing folic acid receptor. Int J Pharm 625, 122064 (2022).","journal-title":"Int J Pharm"},{"issue":"1","key":"38700_CR46","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1186\/s13048-016-0230-2","volume":"9","author":"H Zhang","year":"2016","unstructured":"Zhang, H. et al. Folic acid-targeted iron oxide nanoparticles as contrast agents for magnetic resonance imaging of human ovarian cancer. J. Ovarian Res. 9(1), 19 (2016).","journal-title":"J. Ovarian Res."},{"issue":"26","key":"38700_CR47","doi-asserted-by":"publisher","first-page":"22214","DOI":"10.1021\/acsomega.9b03594","volume":"4","author":"A Angelopoulou","year":"2019","unstructured":"Angelopoulou, A., Kolokithas-Ntoukas, A., Fytas, C. & Avgoustakis, K. Folic acid-functionalized, condensed magnetic nanoparticles for targeted delivery of doxorubicin to tumor cancer cells overexpressing the folate receptor. ACS Omega 4(26), 22214\u201322227 (2019).","journal-title":"ACS Omega"},{"key":"38700_CR48","doi-asserted-by":"publisher","first-page":"13","DOI":"10.4028\/p-6ytPC9","volume":"40","author":"S Wyantuti","year":"2023","unstructured":"Wyantuti, S., Iskandar, J., Fauzia, R. P. & Bahti, H. H. Optimization of hydrothermal synthesis of dysprosium oxide nanoparticles-attached-polyethyleneglycol template using response surface methodology-Box-Behnken. Nano Hybrids Composit. 40, 13\u201318 (2023).","journal-title":"Nano Hybrids Composit."},{"issue":"1","key":"38700_CR49","doi-asserted-by":"publisher","first-page":"100478","DOI":"10.1016\/j.cjac.2024.100478","volume":"53","author":"RP Fauzia","year":"2025","unstructured":"Fauzia, R. P. et al. Synthesis and characterization of folic acid-modified polyethylene glycol-coated holmium nanoparticles as targeted magnetic resonance imaging agent candidate. Chin. J. Anal. Chem. 53(1), 100478 (2025).","journal-title":"Chin. J. Anal. Chem."},{"key":"38700_CR50","doi-asserted-by":"publisher","first-page":"6471","DOI":"10.1021\/acsanm.1c00987","volume":"4","author":"J Dolai","year":"2021","unstructured":"Dolai, J., Mandal, K. & Jana, N. R. Nanoparticle size effects in biomedical applications. ACS Appl. Nano Mater. 4, 6471\u20136496 (2021).","journal-title":"ACS Appl. Nano Mater."},{"issue":"45","key":"38700_CR51","doi-asserted-by":"publisher","first-page":"13379","DOI":"10.1021\/acs.langmuir.1c02056","volume":"37","author":"DJ Pochapski","year":"2021","unstructured":"Pochapski, D. J., Carvalho dos Santos, C., Leite, G. W., Pulcinelli, S. H. & Santilli, C. V. Zeta potential and colloidal stability predictions for inorganic nanoparticle dispersions: Effects of experimental conditions and electrokinetic models on the interpretation of results. Langmuir 37(45), 13379\u201313389 (2021).","journal-title":"Langmuir"},{"key":"38700_CR52","doi-asserted-by":"publisher","first-page":"927","DOI":"10.1007\/s13346-020-00802-8","volume":"11","author":"RS Elbatanony","year":"2021","unstructured":"Elbatanony, R. S. et al. Afatinib-loaded inhalable PLGA nanoparticles for localized therapy of non-small cell lung cancer (NSCLC)\u2014development and in-vitro efficacy. Drug Deliv. Transl. Res. 11, 927\u2013943 (2021).","journal-title":"Drug Deliv. Transl. Res."},{"issue":"1","key":"38700_CR53","doi-asserted-by":"publisher","first-page":"14010","DOI":"10.1038\/s41598-017-14409-6","volume":"7","author":"R Zairov","year":"2017","unstructured":"Zairov, R. et al. Hydration number: crucial role in nuclear magnetic relaxivity of Gd (III) chelate-based nanoparticles. Sci. Rep. 7(1), 14010 (2017).","journal-title":"Sci. Rep."},{"issue":"5","key":"38700_CR54","doi-asserted-by":"publisher","first-page":"1299","DOI":"10.3390\/molecules26051299","volume":"26","author":"NN Mahmoud","year":"2021","unstructured":"Mahmoud, N. N., Aqabani, H., Hikmat, S. & Abu-Dahab, R. Colloidal stability and cytotoxicity of polydopamine-conjugated gold nanorods against prostate cancer cell lines. Molecules 26(5), 1299 (2021).","journal-title":"Molecules"},{"key":"38700_CR55","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1016\/j.jconrel.2016.06.017","volume":"235","author":"S Bhattacharjee","year":"2016","unstructured":"Bhattacharjee, S. DLS and zeta potential - What they are and what they are not?. J. Control. Release 235, 337\u2013351 (2016).","journal-title":"J. Control. Release"},{"key":"38700_CR56","doi-asserted-by":"crossref","unstructured":"Nguyenova, H. Y. et al. Stability and biological response of PEGylated gold nanoparticles. Heliyon 10, (2024).","DOI":"10.1016\/j.heliyon.2024.e30601"},{"key":"38700_CR57","doi-asserted-by":"publisher","first-page":"6287","DOI":"10.1039\/C4CS00487F","volume":"44","author":"TL Moore","year":"2015","unstructured":"Moore, T. L. et al. Nanoparticle colloidal stability in cell culture media and impact on cellular interactions. Chem. Soc. Rev. 44, 6287\u20136305 (2015).","journal-title":"Chem. Soc. Rev."},{"key":"38700_CR58","doi-asserted-by":"publisher","first-page":"16701","DOI":"10.1021\/acsomega.0c01582","volume":"5","author":"G Midekessa","year":"2020","unstructured":"Midekessa, G. et al. Zeta potential of extracellular vesicles: Toward understanding the attributes that determine colloidal stability. ACS Omega 5, 16701\u201316710 (2020).","journal-title":"ACS Omega"},{"issue":"1","key":"38700_CR59","doi-asserted-by":"publisher","first-page":"e0169552","DOI":"10.1371\/journal.pone.0169552","volume":"12","author":"K Strojan","year":"2017","unstructured":"Strojan, K. et al. Dispersion of nanoparticles in different media importantly determines the composition of their protein corona. PLoS ONE 12(1), e0169552 (2017).","journal-title":"PLoS ONE"},{"key":"38700_CR60","doi-asserted-by":"publisher","first-page":"034903","DOI":"10.1063\/5.0011230","volume":"128","author":"A Chaturvedi","year":"2020","unstructured":"Chaturvedi, A. et al. In vitro and ex vivo relaxometric properties of ethylene glycol coated gadolinium oxide nanoparticles for potential use as contrast agents in magnetic resonance imaging. J. Appl. Phys. 128, 034903 (2020).","journal-title":"J. Appl. Phys."},{"issue":"5","key":"38700_CR61","doi-asserted-by":"publisher","first-page":"1159","DOI":"10.3390\/molecules25051159","volume":"25","author":"MY Ahmad","year":"2020","unstructured":"Ahmad, M. Y. et al. In vivo positive magnetic resonance imaging applications of poly (methyl vinyl ether-alt-maleic acid)-coated ultra-small paramagnetic gadolinium oxide nanoparticles. Molecules 25(5), 1159 (2020).","journal-title":"Molecules"},{"issue":"17","key":"38700_CR62","doi-asserted-by":"publisher","first-page":"8222","DOI":"10.3390\/app11178222","volume":"11","author":"S Marasini","year":"2021","unstructured":"Marasini, S. et al. Polyaspartic acid-coated paramagnetic gadolinium oxide nanoparticles as a dual-modal t1 and t2 magnetic resonance imaging contrast agent. Appl. Sci. 11(17), 8222 (2021).","journal-title":"Appl. Sci."},{"key":"38700_CR63","doi-asserted-by":"publisher","first-page":"e13207","DOI":"10.1016\/j.heliyon.2023.e13207","volume":"9","author":"Y Zare","year":"2023","unstructured":"Zare, Y. et al. Synthesis and characterization of folate-functionalized silica-based materials and application for bioimaging of cancer cells. Heliyon 9, e13207 (2023).","journal-title":"Heliyon"},{"key":"38700_CR64","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1016\/j.ejps.2014.04.012","volume":"59","author":"S Gorle","year":"2014","unstructured":"Gorle, S., Ariatti, M. & Singh, M. Novel serum-tolerant lipoplexes target the folate receptor efficiently. Eur. J. Pharm. Sci. 59, 83\u201393 (2014).","journal-title":"Eur. J. Pharm. Sci."},{"issue":"7","key":"38700_CR65","doi-asserted-by":"publisher","first-page":"2401787","DOI":"10.1002\/smll.202401787","volume":"21","author":"R Mallik","year":"2025","unstructured":"Mallik, R. et al. Folate receptor targeting Mn (II) complex encapsulated porous silica nanoparticle as an MRI contrast agent for early-state detection of cancer. Small 21(7), 2401787 (2025).","journal-title":"Small"},{"key":"38700_CR66","doi-asserted-by":"publisher","first-page":"111918","DOI":"10.1016\/j.jphotobiol.2020.111918","volume":"209","author":"CA Monteiro","year":"2020","unstructured":"Monteiro, C. A. et al. Evaluating internalization and recycling of folate receptors in breast cancer cells using quantum dots. J. Photochem. Photobiol. B: Biol. 209, 111918 (2020).","journal-title":"J. Photochem. Photobiol. B: Biol."},{"issue":"3","key":"38700_CR67","doi-asserted-by":"publisher","first-page":"72","DOI":"10.3390\/ph10030072","volume":"10","author":"K Siwowska","year":"2017","unstructured":"Siwowska, K., Schmid, R. M., Cohrs, S., Schibli, R. & M\u00fcller, C. Folate receptor-positive gynecological cancer cells: In vitro and in vivo characterization. Pharmaceuticals 10(3), 72 (2017).","journal-title":"Pharmaceuticals"},{"key":"38700_CR68","doi-asserted-by":"publisher","first-page":"1007","DOI":"10.1021\/mp400659t","volume":"11","author":"NA Bandara","year":"2014","unstructured":"Bandara, N. A., Hansen, M. J. & Low, P. S. Effect of receptor occupancy on folate receptor internalization. Mol. Pharm. 11, 1007\u20131013 (2014).","journal-title":"Mol. Pharm."},{"issue":"3","key":"38700_CR69","doi-asserted-by":"publisher","first-page":"864","DOI":"10.3390\/pharmaceutics15030864","volume":"15","author":"R Daniele","year":"2023","unstructured":"Daniele, R. et al. Influence of folate-targeted gold nanoparticles on subcellular localization and distribution into lysosomes. Pharmaceutics 15(3), 864 (2023).","journal-title":"Pharmaceutics"},{"key":"38700_CR70","first-page":"2023","volume":"6","author":"H Yang","year":"2011","unstructured":"Yang, H. et al. Investigation of folate-conjugated fluorescent silica nanoparticles for targeting delivery to folate receptor-positive tumors and their internalization mechanism. Int. J. Nanomedicine 6, 2023\u20132032 (2011).","journal-title":"Int. J. Nanomedicine"},{"key":"38700_CR71","doi-asserted-by":"publisher","first-page":"1406","DOI":"10.1124\/mol.104.003723","volume":"66","author":"CM Paulos","year":"2004","unstructured":"Paulos, C. M., Reddy, J. A., Leamon, C. P., Turk, M. J. & Low, P. S. Ligand binding and kinetics of folate receptor recycling in vivo: Impact on receptor-mediated drug delivery. Mol. Pharmacol. 66, 1406\u20131414 (2004).","journal-title":"Mol. Pharmacol."},{"key":"38700_CR72","doi-asserted-by":"publisher","first-page":"5497","DOI":"10.1021\/acs.nanolett.3c00665","volume":"23","author":"RK Kawassaki","year":"2023","unstructured":"Kawassaki, R. K. et al. Novel gadolinium-free ultrasmall nanostructured positive contrast for magnetic resonance angiography and imaging. Nano Lett. 23, 5497\u20135505 (2023).","journal-title":"Nano Lett."},{"key":"38700_CR73","doi-asserted-by":"publisher","first-page":"4358","DOI":"10.1021\/acsabm.0c00381","volume":"3","author":"DM Samhadaneh","year":"2020","unstructured":"Samhadaneh, D. M. et al. Evaluation of lanthanide-doped upconverting nanoparticles for in vitro and in vivo applications. ACS Appl. Bio. Mater. 3, 4358\u20134369 (2020).","journal-title":"ACS Appl. Bio. Mater."}],"updated-by":[{"DOI":"10.1038\/s41598-026-70205-1","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T00:00:00Z","timestamp":1788739200000}}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-38700-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-38700-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-38700-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T11:05:13Z","timestamp":1788779113000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-38700-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,7]]},"references-count":73,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["38700"],"URL":"https:\/\/doi.org\/10.1038\/s41598-026-38700-7","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,7]]},"assertion":[{"value":"26 September 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 January 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 August 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 September 2026","order":5,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Correction","order":6,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"A Correction to this paper has been published:","order":7,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"https:\/\/doi.org\/10.1038\/s41598-026-70205-1","URL":"https:\/\/doi.org\/10.1038\/s41598-026-70205-1","order":8,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Ethics"}}],"article-number":"24462"}}