{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T13:57:22Z","timestamp":1790085442872,"version":"4.0.1"},"reference-count":43,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,3,21]],"date-time":"2022-03-21T00:00:00Z","timestamp":1647820800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32000984, 21904135"],"award-info":[{"award-number":["32000984, 21904135"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"the Science Foundation of Jiangsu Province","award":["BK20180250, BE2021665"],"award-info":[{"award-number":["BK20180250, BE2021665"]}]},{"name":"the Project of State Key Laboratory of Radiation Medicine and Protection of Soochow University","award":["GZK1202106"],"award-info":[{"award-number":["GZK1202106"]}]},{"name":"A Project Funded by the Priority Academic Program Development of The Second Affiliated Hospital of Soochow University","award":["XKTJ-XK202006"],"award-info":[{"award-number":["XKTJ-XK202006"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biosensors"],"abstract":"<jats:p>Ovarian cancer (OC) is a lethal disease occurring in women worldwide. Due to the lack of obvious clinical symptoms and sensitivity biomarkers, OC patients are often diagnosed in advanced stages and suffer a poor prognosis. Circulating tumor cells (CTCs), released from tumor sites into the peripheral blood, have been recognized as promising biomarkers in cancer prognosis, treatment monitoring, and metastasis diagnosis. However, the number of CTCs in peripheral blood is low, and it is a technical challenge to isolate, enrich, and identify CTCs from the blood samples of patients. This work develops a simple, effective, and inexpensive strategy to capture and identify CTCs from OC blood samples using the folic acid (FA) and antifouling-hydrogel-modified fluorescent-magnetic nanoparticles. The hydrogel showed a good antifouling property against peripheral blood mononuclear cells (PBMCs). The FA was coupled to the hydrogel surface as the targeting molecule for the CTC isolation, held a good capture efficiency for SK-OV-3 cells (95.58%), and successfully isolated 2\u201312 CTCs from 10 OC patients\u2019 blood samples. The FA-modified fluorescent-magnetic nanoparticles were successfully used for the capture and direct identification of CTCs from the blood samples of OC patients.<\/jats:p>","DOI":"10.3390\/bios12030184","type":"journal-article","created":{"date-parts":[[2022,3,21]],"date-time":"2022-03-21T13:24:59Z","timestamp":1647869099000},"page":"184","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Folic Acid-Modified Fluorescent-Magnetic Nanoparticles for Efficient Isolation and Identification of Circulating Tumor Cells in Ovarian Cancer"],"prefix":"10.3390","volume":"12","author":[{"given":"Yue","family":"Pan","sequence":"first","affiliation":[{"name":"Department of Gynecology and Obstetrics, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China"},{"name":"CAS Key Laboratory for Nano-Bio Interface, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou 215123, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4378-9323","authenticated-orcid":false,"given":"Zhili","family":"Wang","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory for Nano-Bio Interface, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou 215123, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jialing","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China"},{"name":"CAS Key Laboratory for Nano-Bio Interface, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou 215123, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tongping","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China"},{"name":"CAS Key Laboratory for Nano-Bio Interface, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou 215123, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeen","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China"},{"name":"CAS Key Laboratory for Nano-Bio Interface, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou 215123, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pi","family":"Ding","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory for Nano-Bio Interface, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou 215123, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Sun","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory for Nano-Bio Interface, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou 215123, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lifen","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renjun","family":"Pei","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory for Nano-Bio Interface, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou 215123, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weipei","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.canlet.2019.10.014","article-title":"Liquid biopsy in ovarian cancer using circulating tumor DNA and cells: Ready for prime time?","volume":"468","author":"Asante","year":"2020","journal-title":"Cancer Lett."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1240","DOI":"10.1016\/S0140-6736(18)32552-2","article-title":"Epithelial ovarian cancer","volume":"393","author":"Lheureux","year":"2019","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1177\/1179299X19860815","article-title":"Chemotherapy resistance in advanced ovarian cancer patients","volume":"11","author":"Pokhriyal","year":"2019","journal-title":"Biomark. Cancer"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2038","DOI":"10.1039\/C6CS00803H","article-title":"Current detection technologies for circulating tumor cells","volume":"46","author":"Shen","year":"2017","journal-title":"Chem. Soc. Rev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1186\/s13045-019-0735-4","article-title":"Technologies for circulating tumor cell separation from whole blood","volume":"12","author":"Lee","year":"2019","journal-title":"J. Hematol. Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3303","DOI":"10.1038\/s41467-020-17150-3","article-title":"Pancreatic circulating tumor cell profiling identifies LIN28B as a metastasis driver and drug target","volume":"11","author":"Franses","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1803531","DOI":"10.1002\/adfm.201803531","article-title":"Platelet-leukocyte hybrid membrane-coated immunomagnetic beads for highly efficient and highly specific isolation of circulating tumor cells","volume":"28","author":"Rao","year":"2018","journal-title":"Adv. Funct. Mater."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Lux, A., Bott, H., Malek, N.P., Zengerle, R., Maucher, T., and Hoffmann, J. (2021). Real-time detection of tumor cells during capture on a filter element significantly enhancing detection rate. Biosensors, 11.","DOI":"10.3390\/bios11090312"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1016\/j.ccell.2020.03.012","article-title":"Liquid biopsy-based biomarkers of treatment response and resistance","volume":"37","author":"Kilgour","year":"2020","journal-title":"Cancer Cell"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1452","DOI":"10.1039\/C7LC00038C","article-title":"Biophysical isolation and identification of circulating tumor cells","volume":"17","author":"Che","year":"2017","journal-title":"Lab. Chip"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"16354","DOI":"10.1039\/C5NR04798F","article-title":"A 3D graphene oxide microchip and an Au-enwrapped silica nanocomposite-based supersandwich cytosensor toward capture and analysis of circulating tumor cells","volume":"7","author":"Li","year":"2015","journal-title":"Nanoscale"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2918","DOI":"10.1039\/C9AY00646J","article-title":"Detection of circulating tumor cells based on improved SERS-active magnetic nanoparticles","volume":"11","author":"Xue","year":"2019","journal-title":"Anal. Methods"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1478","DOI":"10.1038\/s41467-019-09439-9","article-title":"A temporary indwelling intravascular aphaeretic system for in vivo enrichment of circulating tumor cells","volume":"10","author":"Kim","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"16787","DOI":"10.1021\/acs.analchem.1c03167","article-title":"Dynamic monitoring of EMT in CTCs as an indicator of cancer metastasis","volume":"93","author":"Zhang","year":"2021","journal-title":"Anal. Chem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"22574","DOI":"10.1039\/D0NR06180H","article-title":"Isolation of DNA aptamers targeting N-cadherin and high-efficiency capture of circulating tumor cells by using dual aptamers","volume":"12","author":"Gao","year":"2020","journal-title":"Nanoscale"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Park, C., Abafogi, A.T., Ponnuvelu, D.V., Song, I., Ko, K., and Park, S. (2021). Enhanced luminescent detection of circulating tumor cells by a 3D printed immunomagnetic concentrator. Biosensors, 11.","DOI":"10.3390\/bios11080278"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Shamloo, A., Ahmad, S., and Momeni, M. (2018). Design and parameter study of integrated microfluidic platform for CTC isolation and enquiry; A Numerical Approach. Biosensors, 8.","DOI":"10.3390\/bios8020056"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"335101","DOI":"10.1088\/1361-6528\/ab176c","article-title":"TiO2 nanopillar arrays coated with gelatin film for efficient capture and undamaged release of circulating tumor cells","volume":"30","author":"Li","year":"2019","journal-title":"Nanotechnology"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2000940","DOI":"10.1002\/advs.202000940","article-title":"In vivo enrichment and elimination of circulating tumor cells by using a black phosphorus and antibody functionalized intravenous catheter","volume":"7","author":"Wang","year":"2020","journal-title":"Adv. Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"52406","DOI":"10.1021\/acsami.1c15838","article-title":"Capture, detection, and simultaneous identification of rare circulating tumor cells based on a rhodamine 6G-loaded metal-organic framework","volume":"13","author":"Li","year":"2021","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2000647","DOI":"10.1002\/advs.202000647","article-title":"Bioinspired DNA nanointerface with anisotropic aptamers for accurate capture of circulating tumor cells","volume":"7","author":"Qin","year":"2020","journal-title":"Adv. Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"8032","DOI":"10.1038\/s41598-019-44401-1","article-title":"Fast and efficient microfluidic cell filter for isolation of circulating tumor cells from unprocessed whole blood of colorectal cancer patients","volume":"9","author":"Oliveira","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Salmon, C., Levermann, J., Neves, R.P.L., Liffers, S.T., Kuhlmann, J.D., Buderath, P., Kimmig, R., and Kasimir-Bauer, S. (2021). Image-based identification and genomic analysis of single circulating tumor cells in high grade serous ovarian cancer patients. Cancers, 13.","DOI":"10.3390\/cancers13153748"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2002259","DOI":"10.1002\/advs.202002259","article-title":"Natural Fish Trap-Like Nanocage for Label-Free Capture of Circulating Tumor Cells","volume":"7","author":"Jiang","year":"2020","journal-title":"Adv. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"4372","DOI":"10.1021\/acs.chemmater.8b01646","article-title":"A Chemical Method for Specific Capture of Circulating Tumor Cells Using Label-Free Polyphenol-Functionalized Films","volume":"30","author":"Yang","year":"2018","journal-title":"Chem. Mater."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"39586","DOI":"10.1021\/acsami.9b14051","article-title":"High-efficiency isolation and rapid identification of heterogeneous circulating tumor cells (CTCs) using dual-antibody-modified fluorescent-magnetic nanoparticles","volume":"11","author":"Wang","year":"2019","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1039\/D0TB02380A","article-title":"Antifouling hydrogel-coated magnetic nanoparticles for selective isolation and recovery of circulating tumor cells","volume":"9","author":"Wang","year":"2021","journal-title":"J. Mater. Chem. B"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3694","DOI":"10.1021\/acsami.0c20916","article-title":"Tannic acid (TA)-functionalized magnetic nanoparticles for EpCAM-independent circulating tumor cell (CTC) isolation from patients with different cancers","volume":"13","author":"Ding","year":"2021","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"14055","DOI":"10.1021\/acsami.8b02583","article-title":"Folic acid targeting for efficient isolation and detection of ovarian cancer CTCs from human whole blood based on two-step binding strategy","volume":"10","author":"Nie","year":"2018","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"5718","DOI":"10.1039\/C9AY02090J","article-title":"A folic acid modified polystyrene nanosphere surface for circulating tumor cell capture","volume":"11","author":"Chen","year":"2019","journal-title":"Anal. Methods"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1058","DOI":"10.2174\/138161212799315777","article-title":"Folate based radiopharmaceuticals for imaging and therapy of cancer and inflammation","volume":"18","author":"Muller","year":"2012","journal-title":"Curr. Pharm. Des."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.2147\/OTT.S40947","article-title":"Targeted drug delivery via folate receptors in recurrent ovarian cancer: A review","volume":"7","author":"Marchetti","year":"2014","journal-title":"OncoTargets Ther."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"8836","DOI":"10.1021\/am501626t","article-title":"Fe3O4\/PVIM-Ni2+ magnetic composite microspheres for highly specific separation of histidine-rich proteins","volume":"6","author":"Zhang","year":"2014","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2212","DOI":"10.1039\/D0TB02988B","article-title":"A PLGA nanofiber microfluidic device for highly efficient isolation and release of different phenotypic circulating tumor cells based on dual aptamers","volume":"9","author":"Wu","year":"2021","journal-title":"J. Mater. Chem. B"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/S0168-3659(03)00215-3","article-title":"Immunotherapy of folate receptor-expressing tumors: Review of recent advances and future prospects","volume":"91","author":"Lu","year":"2003","journal-title":"J. Control Release"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1361","DOI":"10.1039\/b903428e","article-title":"Evaluation of specific delivery of chimeric phi29 pRNA\/siRNA nanoparticles to multiple tumor cells","volume":"5","author":"Li","year":"2009","journal-title":"Mol. Biosyst."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1387","DOI":"10.1002\/cmdc.200800125","article-title":"Targeting the folate receptor (FR): Imaging and cytotoxicity of ReI conjugates in FR-overexpressing cancer cells","volume":"3","author":"Rabideau","year":"2008","journal-title":"Chem. Med. Chem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"8548","DOI":"10.1016\/j.biomaterials.2011.07.067","article-title":"Folate-targeted nanoparticle delivery of chemo- and radiotherapeutics for the treatment of ovarian cancer peritoneal metastasis","volume":"32","author":"Werner","year":"2011","journal-title":"Biomaterials"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1089\/hyb.2007.0512","article-title":"A novel monoclonal antibody for detection of folate receptor alpha in paraffin-embedded tissues","volume":"26","author":"Smith","year":"2007","journal-title":"Hybridoma"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"116453","DOI":"10.1016\/j.trac.2021.116453","article-title":"Magnetic particles as promising circulating tumor cell catchers assisting liquid biopsy in cancer diagnosis: A review","volume":"145","author":"Li","year":"2021","journal-title":"Trend. Anal. Chem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"9971","DOI":"10.1039\/D0TB01091J","article-title":"Nondestructive capture, release, and detection of circulating tumor cells with cystamine-mediated folic acid decorated magnetic nanospheres","volume":"8","author":"Li","year":"2020","journal-title":"J. Mater. Chem. B"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1126\/science.1253533","article-title":"Ex vivo culture of circulating breast tumor cells for individualized testing of drug susceptibility","volume":"345","author":"Yu","year":"2014","journal-title":"Science"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2250","DOI":"10.1364\/BOE.417525","article-title":"Photoacoustic tomography reconstruction using lag-based delay multiply and sum with a coherence factor improves in vivo ovarian cancer diagnosis","volume":"12","author":"Yang","year":"2021","journal-title":"Biomed. Opt. Express"}],"container-title":["Biosensors"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-6374\/12\/3\/184\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:40:21Z","timestamp":1760136021000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-6374\/12\/3\/184"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,21]]},"references-count":43,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2022,3]]}},"alternative-id":["bios12030184"],"URL":"https:\/\/doi.org\/10.3390\/bios12030184","relation":{},"ISSN":["2079-6374"],"issn-type":[{"value":"2079-6374","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,21]]}}}