{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T17:20:34Z","timestamp":1776792034202,"version":"3.51.2"},"reference-count":69,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2020,6,3]],"date-time":"2020-06-03T00:00:00Z","timestamp":1591142400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004837","name":"Ministerio de Ciencia e Innovaci\u00f3n","doi-asserted-by":"publisher","award":["RTI2018-094322-B-I00"],"award-info":[{"award-number":["RTI2018-094322-B-I00"]}],"id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004837","name":"Ministerio de Ciencia e Innovaci\u00f3n","doi-asserted-by":"publisher","award":["CTQ2017-90802-REDT"],"award-info":[{"award-number":["CTQ2017-90802-REDT"]}],"id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"publisher"}]},{"name":"CNCS - UEFISCDI","award":["PN-III-P4-ID-PCCF-2016-0142"],"award-info":[{"award-number":["PN-III-P4-ID-PCCF-2016-0142"]}]},{"name":"Direcci\u00f3n General de Investigaci\u00f3n e Innovaci\u00f3n, Consejer\u00eda de Educaci\u00f3n e Investigaci\u00f3n de la Comunidad de Madrid","award":["PEJD-2017-PRE\/BMD-3512"],"award-info":[{"award-number":["PEJD-2017-PRE\/BMD-3512"]}]},{"name":"Escuela Internacional de Doctorado of the Universidad Rey Juan Carlos","award":["Mobility Grant"],"award-info":[{"award-number":["Mobility Grant"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>The synthesis, characterization and cytotoxic activity against different cancer cell lines of various mesoporous silica-based materials containing folate targeting moieties and a cytotoxic fragment based on a triphenyltin(IV) derivative have been studied. Two different mesoporous nanostructured silica systems have been used: firstly, micronic silica particles of the MSU-2 type and, secondly, mesoporous silica nanoparticles (MSNs) of about 80 nm. Both series of materials have been characterized by different methods, such as powder X-ray diffraction, X-ray fluorescence, absorption spectroscopy and microscopy. In addition, these systems have been tested against four different cancer cell lines, namely, OVCAR-3, DLD-1, A2780 and A431, in order to observe if the size of the silica-based systems and the quantity of incorporated folic acid influence their cytotoxic action. The results show that the materials are more active when the quantity of folic acid is higher, especially in those cells that overexpress folate receptors such as OVCAR-3 and DLD-1. In addition, the study of the potential modulation of the soluble folate receptor alpha (FOLR1) by treatment with the synthesized materials has been carried out using OVCAR-3, DLD-1, A2780 and A431 tumour cell lines. The results show that a relatively high concentration of folic acid functionalization of the nanostructured silica together with the incorporation of the cytotoxic tin fragment leads to an increase in the quantity of the soluble FOLR1 secreted by the tumour cells. In addition, the studies reported here show that this increase of the soluble FOLR1 occurs presumably by cutting the glycosyl-phosphatidylinositol anchor of membrane FR-\u03b1 and by the release of intracellular FR-\u03b1. This study validates the potential use of a combination of mesoporous silica materials co-functionalized with folate targeting molecules and an organotin(IV) drug as a strategy for the therapeutic treatment of several cancer cells overexpressing folate receptors.<\/jats:p>","DOI":"10.3390\/pharmaceutics12060512","type":"journal-article","created":{"date-parts":[[2020,6,4]],"date-time":"2020-06-04T04:36:09Z","timestamp":1591245369000},"page":"512","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Role of Folic Acid in the Therapeutic Action of Nanostructured Porous Silica Functionalized with Organotin(IV) Compounds against Different Cancer Cell Lines"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3057-4905","authenticated-orcid":false,"given":"Diana","family":"D\u00edaz-Garc\u00eda","sequence":"first","affiliation":[{"name":"COMET-NANO Group, Departamento de Biolog\u00eda y Geolog\u00eda, F\u00edsica y Qu\u00edmica Inorg\u00e1nica, ESCET, Universidad Rey Juan Carlos, 28933 M\u00f3stoles, Spain"},{"name":"Tumour Biology Department, the Institute of Oncology \u201cProf. Dr. I. Chiricuta\u201d, RO-400015 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karla","family":"Montalb\u00e1n-Hern\u00e1ndez","sequence":"additional","affiliation":[{"name":"COMET-NANO Group, Departamento de Biolog\u00eda y Geolog\u00eda, F\u00edsica y Qu\u00edmica Inorg\u00e1nica, ESCET, Universidad Rey Juan Carlos, 28933 M\u00f3stoles, Spain"},{"name":"Innate Immunity Group, Laboratory of Tumour Immunology, IdiPAZ Institute for Health Research, La Paz University Hospital, 28046 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irene","family":"Mena-Palomo","sequence":"additional","affiliation":[{"name":"COMET-NANO Group, Departamento de Biolog\u00eda y Geolog\u00eda, F\u00edsica y Qu\u00edmica Inorg\u00e1nica, ESCET, Universidad Rey Juan Carlos, 28933 M\u00f3stoles, Spain"},{"name":"Innate Immunity Group, Laboratory of Tumour Immunology, IdiPAZ Institute for Health Research, La Paz University Hospital, 28046 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9928-5883","authenticated-orcid":false,"given":"Patriciu","family":"Achimas-Cadariu","sequence":"additional","affiliation":[{"name":"Department of Surgery, the Institute of Oncology \u201cProf. Dr. I. Chiricuta\u201d, RO-400015 Cluj-Napoca, Romania"},{"name":"Department of Surgery and Gynecological Oncology, the University of Medicine and Pharmacy \u201cIuliu Hatieganu\u201d, RO-400337 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3198-5378","authenticated-orcid":false,"given":"Antonio","family":"Rodr\u00edguez-Di\u00e9guez","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica Inorg\u00e1nica, Universidad de Granada, Facultad de Ciencias, Campus de Fuentenueva, Avda. Fuentenueva s\/n, E-18071 Granada, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1957-877X","authenticated-orcid":false,"given":"Eduardo","family":"L\u00f3pez-Collazo","sequence":"additional","affiliation":[{"name":"Innate Immunity Group, Laboratory of Tumour Immunology, IdiPAZ Institute for Health Research, La Paz University Hospital, 28046 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6588-878X","authenticated-orcid":false,"given":"Sanjiv","family":"Prashar","sequence":"additional","affiliation":[{"name":"COMET-NANO Group, Departamento de Biolog\u00eda y Geolog\u00eda, F\u00edsica y Qu\u00edmica Inorg\u00e1nica, ESCET, Universidad Rey Juan Carlos, 28933 M\u00f3stoles, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karina","family":"Ovejero Paredes","sequence":"additional","affiliation":[{"name":"Nanobiotechnology for Life Sciences Group, Department of Chemistry in Pharmaceutical Sciences, Faculty of Pharmacy, Universidad Complutense de Madrid (UCM), Plaza Ram\u00f3n y Cajal s\/n, E-28040 Madrid, Spain"},{"name":"Microscopy and Dynamic Imaging Unit, Fundaci\u00f3n Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Calle Melchor Fernandez Almagro 3, E-28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8142-4566","authenticated-orcid":false,"given":"Marco","family":"Filice","sequence":"additional","affiliation":[{"name":"Nanobiotechnology for Life Sciences Group, Department of Chemistry in Pharmaceutical Sciences, Faculty of Pharmacy, Universidad Complutense de Madrid (UCM), Plaza Ram\u00f3n y Cajal s\/n, E-28040 Madrid, Spain"},{"name":"Microscopy and Dynamic Imaging Unit, Fundaci\u00f3n Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Calle Melchor Fernandez Almagro 3, E-28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0898-0547","authenticated-orcid":false,"given":"Eva","family":"Fischer-Fodor","sequence":"additional","affiliation":[{"name":"Tumour Biology Department, the Institute of Oncology \u201cProf. Dr. I. Chiricuta\u201d, RO-400015 Cluj-Napoca, Romania"},{"name":"Medfuture-Research Center for Advanced Medicine, the University of Medicine and Pharmacy \u201cIuliu Hatieganu\u201d, RO-400337 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9538-8359","authenticated-orcid":false,"given":"Santiago","family":"G\u00f3mez-Ruiz","sequence":"additional","affiliation":[{"name":"COMET-NANO Group, Departamento de Biolog\u00eda y Geolog\u00eda, F\u00edsica y Qu\u00edmica Inorg\u00e1nica, ESCET, Universidad Rey Juan Carlos, 28933 M\u00f3stoles, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,6,3]]},"reference":[{"key":"ref_1","unstructured":"(2020, April 04). Worldwide Cancer Statistics. Available online: https:\/\/www.cancerresearchuk.org\/health-professional\/cancer-statistics\/worldwide-cancer."},{"key":"ref_2","unstructured":"(2020, April 04). Cancer Tomorrow. Available online: http:\/\/gco.iarc.fr\/tomorrow\/home."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1002\/ijc.28940","article-title":"Personalised cancer medicine","volume":"137","author":"Jackson","year":"2015","journal-title":"Int. J. Cancer"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Dumbrava, E.I., and Meric-Bernstam, F. (2018). Personalized cancer therapy\u2014Leveraging a knowledge base for clinical decision-making. Cold Spring Harb. Mol. Case Stud., 4.","DOI":"10.1101\/mcs.a001578"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"62742","DOI":"10.18632\/oncotarget.18409","article-title":"Improving radiotherapy in cancer treatment: Promises and challenges","volume":"8","author":"Chen","year":"2017","journal-title":"Oncotarget"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1146\/annurev-cancerbio-030617-050512","article-title":"Hormone-Targeted Therapy and Resistance","volume":"2","author":"Metcalfe","year":"2018","journal-title":"Annu. Rev. Cancer Biol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"407","DOI":"10.3892\/ijo.2018.4661","article-title":"From chemotherapy to biological therapy: A review of novel concepts to reduce the side effects of systemic cancer treatment","volume":"54","author":"Schirrmacher","year":"2019","journal-title":"Int. J. Oncol."},{"key":"ref_8","first-page":"1799","article-title":"The successful regression of large solid sarcoma 180 tumors by platinum compounds","volume":"30","author":"Rosenberg","year":"1970","journal-title":"Cancer Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"599","DOI":"10.2147\/DDDT.S119488","article-title":"Metal complexes in cancer therapy\u2014An update from drug design perspective","volume":"11","author":"Ndagi","year":"2017","journal-title":"Drug. Des. Dev. Ther."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"4540","DOI":"10.1021\/cr400460s","article-title":"Metallodrugs in medicinal inorganic chemistry","volume":"114","author":"Mjos","year":"2014","journal-title":"Chem. Rev."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.ccr.2016.01.001","article-title":"Nanostructured materials functionalized with metal complexes: In search of alternatives for administering anticancer metallodrugs","volume":"312","author":"Wani","year":"2016","journal-title":"Coord. Chem. Rev."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Ellahioui, Y., Prashar, S., and G\u00f3mez-Ruiz, S. (2017). Anticancer Applications and Recent Investigations of Metallodrugs Based on Gallium, Tin and Titanium. Inorganics, 5.","DOI":"10.3390\/inorganics5010004"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Poursharifi, M., Wlodarczyk, M.T., and Mieszawska, A.J. (2019). Nano-Based Systems and Biomacromolecules as Carriers for Metallodrugs in Anticancer Therapy. Inorganics, 7.","DOI":"10.3390\/inorganics7010002"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"4450","DOI":"10.2174\/0929867323666161024153459","article-title":"A Short Overview on the Biomedical Applications of Silica, Alumina and Calcium Phosphate-based Nanostructured Materials","volume":"23","author":"Ellahioui","year":"2016","journal-title":"Curr. Med. Chem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"5588","DOI":"10.1002\/chem.200900151","article-title":"A New Generation of Anticancer Drugs: Mesoporous Materials Modified with Titanocene Complexes","volume":"15","author":"Sierra","year":"2009","journal-title":"Chem. Eur. J."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2597","DOI":"10.1039\/b920051g","article-title":"Improvement of cytotoxicity of titanocene-functionalized mesoporous materials by the increase of the titanium content","volume":"39","author":"Zizak","year":"2010","journal-title":"Dalton Trans."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1039\/B919269G","article-title":"Study of the influence of the metal complex on the cytotoxic activity of titanocene-functionalized mesoporous materials","volume":"20","author":"Sierra","year":"2010","journal-title":"J. Mater. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.jinorgbio.2011.09.033","article-title":"Study of the cytotoxicity and particle action in human cancer cells of titanocene-functionalized materials with potential application against tumors","volume":"106","author":"Paschke","year":"2012","journal-title":"J. Inorg. Biochem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"5982","DOI":"10.1002\/anie.201400763","article-title":"Organotin(IV)-loaded mesoporous silica as a biocompatible strategy in cancer treatment","volume":"53","author":"Bensing","year":"2014","journal-title":"Angew. Chem. Int. Ed. Engl."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"10811","DOI":"10.1002\/chem.201400300","article-title":"Anti-cancer Applications of Titanocene-Functionalised Nanostructured Systems: An Insight into Cell Death Mechanisms","volume":"20","author":"Virag","year":"2014","journal-title":"Chem. Eur. J."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2522","DOI":"10.1021\/om5012209","article-title":"Ether-Substituted Group 4 Metallocene Complexes: Cytostatic Effects and Applications in Ethylene Polymerization","volume":"34","author":"Prashar","year":"2015","journal-title":"Organometallics"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"18984","DOI":"10.1039\/C6DT03519A","article-title":"Evaluation of functionalized mesoporous silica SBA-15 as a carrier system for Ph3Sn(CH2)3OH against the A2780 ovarian carcinoma cell line","volume":"45","author":"Bensing","year":"2016","journal-title":"Dalton Trans."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"12284","DOI":"10.1039\/C8DT01677A","article-title":"Modulation of the mechanism of apoptosis in cancer cell lines by treatment with silica-based nanostructured materials functionalized with different metallodrugs","volume":"47","author":"Cenariu","year":"2018","journal-title":"Dalton Trans."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"G\u00f3mez-Ruiz, S., Garc\u00eda-Pe\u00f1as, A., Prashar, S., Rodr\u00edguez-Di\u00e9guez, A., and Fischer-Fodor, E. (2018). Anticancer Applications of Nanostructured Silica-Based Materials Functionalized with Titanocene Derivatives: Induction of Cell Death Mechanism through TNFR1 Modulation. Materials, 11.","DOI":"10.3390\/ma11020224"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"12914","DOI":"10.1039\/C8DT02011F","article-title":"Mesoporous SBA-15 modified with titanocene complexes and ionic liquids: Interactions with DNA and other molecules of biological interest studied by solid state electrochemical techniques","volume":"47","author":"Cruz","year":"2018","journal-title":"Dalton Trans."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"D\u00edaz-Garc\u00eda, D., Ardiles, P.R., Prashar, S., Rodr\u00edguez-Di\u00e9guez, A., P\u00e1ez, P.L., and G\u00f3mez-Ruiz, S. (2019). Preparation and Study of the Antibacterial Applications and Oxidative Stress Induction of Copper Maleamate-Functionalized Mesoporous Silica Nanoparticles. Pharmaceutics, 11.","DOI":"10.3390\/pharmaceutics11010030"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"5940","DOI":"10.1039\/C8DT02392A","article-title":"Mesoporous silica nanoparticles functionalised with a photoactive ruthenium(ii) complex: Exploring the formulation of a metal-based photodynamic therapy photosensitiser","volume":"48","author":"Ellahioui","year":"2019","journal-title":"Dalton Trans."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"111031","DOI":"10.1039\/C6RA22596A","article-title":"SBA-15 mesoporous silica particles loaded with cisplatin induce senescence in B16F10 cells","volume":"6","author":"Edeler","year":"2016","journal-title":"RSC Adv."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.jinorgbio.2016.11.004","article-title":"Inorganic mesoporous silicas as vehicles of two novel anthracene-based ruthenium metalloarenes","volume":"166","author":"Rojas","year":"2017","journal-title":"J. Inorg. Biochem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.jinorgbio.2017.12.011","article-title":"Delivery of [Ru(\u03b76-p-cymene)Cl2{Ph2P(CH2)3SPh-\u03baP}] using unfunctionalized and mercapto functionalized SBA-15 mesoporous silica: Preparation, characterization and in vitro study","volume":"180","author":"Edeler","year":"2018","journal-title":"J. Inorg. Biochem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1007\/s00775-019-01640-x","article-title":"The interaction between SBA-15 derivative loaded with Ph3Sn(CH2)6OH and human melanoma A375 cell line: Uptake and stem phenotype loss","volume":"24","author":"Edeler","year":"2019","journal-title":"J. Biol. Inorg. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/j.msec.2019.03.010","article-title":"Impact of the mesoporous silica SBA-15 functionalization on the mode of action of Ph3Sn(CH2)6OH","volume":"100","author":"Edeler","year":"2019","journal-title":"Mater. Sci. Eng. C"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"110154","DOI":"10.1016\/j.micromeso.2020.110154","article-title":"Mesoporous silica nanoparticles functionalized with a dialkoxide diorganotin(IV) compound: In search of more selective systems against cancer cells","volume":"300","author":"Sommerova","year":"2020","journal-title":"Microporous Mesoporous Mater."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Ovejero Paredes, K., D\u00edaz-Garc\u00eda, D., Garc\u00eda-Almod\u00f3var, V., Lozano Chamizo, L., Marciello, M., D\u00edaz-S\u00e1nchez, M., Prashar, S., G\u00f3mez-Ruiz, S., and Filice, M. (2020). Multifunctional Silica-Based Nanoparticles with Controlled Release of Organotin Metallodrug for Targeted Theranosis of Breast Cancer. Cancers, 12.","DOI":"10.3390\/cancers12010187"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"455102","DOI":"10.1088\/0957-4484\/22\/45\/455102","article-title":"Targeted anticancer prodrug with mesoporous silica nanoparticles as vehicles","volume":"22","author":"Fan","year":"2011","journal-title":"Nanotechnology"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1016\/j.nano.2011.06.002","article-title":"In vivo tumor suppression efficacy of mesoporous silica nanoparticles-based drug-delivery system: Enhanced efficacy by folate modification","volume":"8","author":"Lu","year":"2012","journal-title":"Nanomedicine"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"7315","DOI":"10.2147\/OTT.S113815","article-title":"Mesoporous silica nanoparticles functionalized with folic acid\/methionine for active targeted delivery of docetaxel","volume":"9","author":"Khosravian","year":"2016","journal-title":"Onco Targets Ther."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"7061","DOI":"10.1039\/C5RA22937E","article-title":"Hydroxylated fullerene-capped, vinblastine-loaded folic acid-functionalized mesoporous silica nanoparticles for targeted anticancer therapy","volume":"6","author":"Cunin","year":"2016","journal-title":"RSC Adv."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"26511","DOI":"10.1021\/acsami.6b08400","article-title":"Rational Design of Multifunctional Dendritic Mesoporous Silica Nanoparticles to Load Curcumin and Enhance Efficacy for Breast Cancer Therapy","volume":"8","author":"Wang","year":"2016","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/j.jddst.2017.07.025","article-title":"A targeted drug delivery system of anti-cancer agents based on folic acid-cyclodextrin-long polymer functionalized silica nanoparticles","volume":"41","author":"Khattabi","year":"2017","journal-title":"J. Drug Deliv. Sci. Technol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"21673","DOI":"10.1021\/acsami.7b05278","article-title":"Dacarbazine-Loaded Hollow Mesoporous Silica Nanoparticles Grafted with Folic Acid for Enhancing Antimetastatic Melanoma Response","volume":"9","author":"Liu","year":"2017","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"4379","DOI":"10.2147\/IJN.S142668","article-title":"Folic acid-conjugated mesoporous silica nanoparticles for enhanced therapeutic efficacy of topotecan in retina cancers","volume":"13","author":"Qu","year":"2018","journal-title":"Int. J. Nanomed."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/j.biomaterials.2018.07.030","article-title":"Folate-conjugated nanobubbles selectively target and kill cancer cells via ultrasound-triggered intracellular explosion","volume":"181","author":"Shen","year":"2018","journal-title":"Biomaterials"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"3614","DOI":"10.1021\/acssuschemeng.8b06586","article-title":"Dual-Targeted Controlled Delivery Based on Folic Acid Modified Pectin-Based Nanoparticles for Combination Therapy of Liver Cancer","volume":"7","author":"Liu","year":"2019","journal-title":"ACS Sustain. Chem. Eng."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Poltavets, Y.I., Zhirnik, A.S., Zavarzina, V.V., Semochkina, Y.P., Shuvatova, V.G., Krasheninnikova, A.A., Aleshin, S.V., Dronov, D.O., Vorontsov, E.A., and Balabanyan, V.Y. (2019). In vitro anticancer activity of folate-modified docetaxel-loaded PLGA nanoparticles against drug-sensitive and multidrug-resistant cancer cells. Cancer Nanotechnol., 10.","DOI":"10.1186\/s12645-019-0048-x"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"109323","DOI":"10.1016\/j.biopha.2019.109323","article-title":"Folate-coated, long-circulating and pH-sensitive liposomes enhance doxorubicin antitumor effect in a breast cancer animal model","volume":"118","author":"Fernandes","year":"2019","journal-title":"Biomed. Pharmacother."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"3389","DOI":"10.2147\/IJN.S198848","article-title":"Controlled drug delivery systems for cancer based on mesoporous silica nanoparticles","volume":"14","author":"Fanarraga","year":"2019","journal-title":"Int. J. Nanomed."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1016\/j.molliq.2018.07.024","article-title":"Preparation of folic acid-conjugated dendritic mesoporous silica nanoparticles for pH-controlled release and targeted delivery of a cyclometallated gold(III) complex as an antitumor agent","volume":"265","author":"Malekmohammadi","year":"2018","journal-title":"J. Mol. Liq."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1039\/C7SC04004K","article-title":"Advances in targeting the folate receptor in the treatment\/imaging of cancers","volume":"9","author":"Javaid","year":"2018","journal-title":"Chem. Sci."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"938","DOI":"10.1002\/ijc.22811","article-title":"Folate receptor overexpression is associated with poor outcome in breast cancer","volume":"121","author":"Hartmann","year":"2007","journal-title":"Int. J. Cancer"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"15180","DOI":"10.1073\/pnas.1308827110","article-title":"Structures of human folate receptors reveal biological trafficking states and diversity in folate and antifolate recognition","volume":"110","author":"Wibowo","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"337","DOI":"10.4110\/in.2016.16.6.337","article-title":"Folate Receptor-Targeted Diagnostics and Therapeutics for Inflammatory Diseases","volume":"16","author":"Yi","year":"2016","journal-title":"Immune Netw."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"183","DOI":"10.3322\/caac.20113","article-title":"Recent progress in the diagnosis and treatment of ovarian cancer","volume":"61","author":"Jelovac","year":"2011","journal-title":"CA Cancer J. Clin."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1356","DOI":"10.1016\/j.cellsig.2015.03.020","article-title":"Folic acid mediates activation of the pro-oncogene STAT3 via the Folate Receptor alpha","volume":"27","author":"Hansen","year":"2015","journal-title":"Cell Signal."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Kelemen, L.E., Brenton, J.D., Parkinson, C., Whitaker, H.C., Piskorz, A.M., Csizmadi, I., and Robson, P.J. (2014). Conditions Associated with Circulating Tumor-Associated Folate Receptor 1 Protein in Healthy Men and Women. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0096542"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Basal, E., Eghbali-Fatourechi, G.Z., Kalli, K.R., Hartmann, L.C., Goodman, K.M., Goode, E.L., Kamen, B.A., Low, P.S., and Knutson, K.L. (2009). Functional folate receptor alpha is elevated in the blood of ovarian cancer patients. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0006292"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1462","DOI":"10.1016\/j.clinbiochem.2013.03.010","article-title":"Folate-receptor 1 (FOLR1) protein is elevated in the serum of ovarian cancer patients","volume":"46","author":"Leung","year":"2013","journal-title":"Clin. Biochem."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1038\/bjc.1996.91","article-title":"Role of membrane folate-binding protein in the cytotoxicity of 5,10-dideazatetrahydrofolic acid in human ovarian carcinoma cell lines in vitro","volume":"73","author":"Sen","year":"1996","journal-title":"Br. J. Cancer"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1188","DOI":"10.1038\/s41598-018-19391-1","article-title":"Combined use of EpCAM and FR\u03b1 enables the high-efficiency capture of circulating tumor cells in non-small cell lung cancer","volume":"8","author":"Chen","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Tsukihara, H., Tsunekuni, K., and Takechi, T. (2016). Folic Acid-Metabolizing Enzymes Regulate the Antitumor Effect of 5-Fluoro-2\u2032-Deoxyuridine in Colorectal Cancer Cell Lines. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0163961"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1080","DOI":"10.1158\/1078-0432.CCR-03-0157","article-title":"The role of alpha-folate receptor-mediated transport in the antitumor activity of antifolate drugs","volume":"10","author":"Theti","year":"2004","journal-title":"Clin. Cancer Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"8398","DOI":"10.1021\/ja901831u","article-title":"Mesoporous Silica Nanoparticle-Based Double Drug Delivery System for Glucose-Responsive Controlled Release of Insulin and Cyclic AMP","volume":"131","author":"Zhao","year":"2009","journal-title":"J. Am. Chem. Soc."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"4901","DOI":"10.1166\/jnn.2009.1106","article-title":"Synthesis and characterization of novel mesoporous silicas of the MSU-X family for environmental applications","volume":"9","author":"Fajardo","year":"2009","journal-title":"J. Nanosci. Nanotechnol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1016\/j.msec.2016.03.011","article-title":"Curcumin-loaded silica-based mesoporous materials: Synthesis, characterization and cytotoxic properties against cancer cells","volume":"63","author":"Bollu","year":"2016","journal-title":"Mater. Sci. Eng. C Mater. Biol. Appl."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1039\/C5BM00552C","article-title":"Curcumin loaded mesoporous silica: An effective drug delivery system for cancer treatment","volume":"4","author":"Kotcherlakota","year":"2016","journal-title":"Biomater. Sci."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"8718","DOI":"10.1039\/C6CE01810F","article-title":"Multifunctional applications of a dysprosium-based metal\u2013organic chain with single-ion magnet behaviour","volume":"18","author":"Oyarzabal","year":"2016","journal-title":"CrystEngComm"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.1515\/pac-2014-1117","article-title":"Physisorption of gases, with special reference to the evaluation of surface area and pore size distribution (IUPAC Technical Report)","volume":"87","author":"Thommes","year":"2015","journal-title":"Pure Appl. Chem."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/j.phymed.2018.06.019","article-title":"Augmented cytotoxic effects of paclitaxel by curcumin induced overexpression of folate receptor-\u03b1 for enhanced targeted drug delivery in HeLa cells","volume":"56","author":"Dhanasekaran","year":"2019","journal-title":"Phytomedicine"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1080\/15384047.2017.1395118","article-title":"In Vitro and In Vivo evaluation of a novel folate-targeted theranostic nanoemulsion of docetaxel for imaging and improved anticancer activity against ovarian cancers","volume":"19","author":"Patel","year":"2018","journal-title":"Cancer Biol. Ther."}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/12\/6\/512\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:35:27Z","timestamp":1760175327000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/12\/6\/512"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,6,3]]},"references-count":69,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2020,6]]}},"alternative-id":["pharmaceutics12060512"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics12060512","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,6,3]]}}}