{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T13:56:36Z","timestamp":1791640596180,"version":"4.3.4"},"reference-count":128,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2022,8,23]],"date-time":"2022-08-23T00:00:00Z","timestamp":1661212800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Stimulus to Excellence for Permanent University Professors","award":["EPU-INV\/2020\/012"],"award-info":[{"award-number":["EPU-INV\/2020\/012"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Today, cancer treatment is an important issue in the medical world due to the challenges and side effects of ongoing treatment procedures. Current methods can be replaced with targeted nano-drug delivery systems to overcome such side effects. In the present work, an intelligent nano-system consisting of Chitosan (Ch)\/Gamma alumina (\u03b3Al)\/Fe3O4 and 5-Fluorouracil (5-FU) was synthesized and designed for the first time in order to influence the Michigan Cancer Foundation-7 (MCF-7) cell line in the treatment of breast cancer. Physico-chemical characterization of the nanocarriers was carried out using X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), vibrating sample magnetometry (VSM), dynamic light scattering (DLS), and scanning electron microscopy (SEM). SEM analysis revealed smooth and homogeneous spherical nanoparticles. The high stability of the nanoparticles and their narrow size distribution was confirmed by DLS. The results of the loading study demonstrated that these nano-systems cause controlled, stable, and pH-sensitive release in cancerous environments with an inactive targeting mechanism. Finally, the results of MTT and flow cytometry tests indicated that this nano-system increased the rate of apoptosis induction on cancerous masses and could be an effective alternative to current treatments.<\/jats:p>","DOI":"10.3390\/molecules27175369","type":"journal-article","created":{"date-parts":[[2022,8,24]],"date-time":"2022-08-24T00:22:48Z","timestamp":1661300568000},"page":"5369","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":79,"title":["Chitosan\/Gamma-Alumina\/Fe3O4@5-FU Nanostructures as Promising Nanocarriers: Physiochemical Characterization and Toxicity Activity"],"prefix":"10.3390","volume":"27","author":[{"given":"Narges","family":"Ajalli","sequence":"first","affiliation":[{"name":"Department of Chemical Engineering, Faculty of Engineering, University of Tehran, Tehran 1417935840, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehrab","family":"Pourmadadi","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering, Faculty of Engineering, University of Tehran, Tehran 1417935840, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatemeh","family":"Yazdian","sequence":"additional","affiliation":[{"name":"Department of Life Science Engineering, Faculty of New Science and Technologies, University of Tehran, Tehran 1439956191, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8460-0841","authenticated-orcid":false,"given":"Hamid","family":"Rashedi","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering, Faculty of Engineering, University of Tehran, Tehran 1417935840, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mona","family":"Navaei-Nigjeh","sequence":"additional","affiliation":[{"name":"Pharmaceutical Sciences Research Center, Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran 1417613151, Iran"},{"name":"Department of Pharmaceutical Biomaterials, Medical Biomaterials Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran 1417614411, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7405-2354","authenticated-orcid":false,"given":"Ana M.","family":"D\u00edez-Pascual","sequence":"additional","affiliation":[{"name":"Universidad de Alcal\u00e1, Facultad de Ciencias, Departamento de Qu\u00edmica Anal\u00edtica, Qu\u00edmica F\u00edsica e Ingenier\u00eda Qu\u00edmica, Ctra. Madrid-Barcelona, Km. 33.6, 28805 Alcal\u00e1 de Henares, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.coi.2015.01.003","article-title":"TCR affinity for p\/MHC formed by tumor antigens that are self-proteins: Impact on efficacy and toxicity","volume":"33","author":"Stone","year":"2015","journal-title":"Curr. Opin. Immunol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1007\/BF02893458","article-title":"Tumor stem cells","volume":"10","author":"Kopper","year":"2004","journal-title":"Pathol. Oncol. Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1038\/s42255-019-0032-0","article-title":"Metabolic signatures of cancer cells and stem cells","volume":"1","author":"Intlekofer","year":"2019","journal-title":"Nat. Metab."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1038\/s41568-020-00320-2","article-title":"The metabolism of cancer cells during metastasis","volume":"21","author":"Bergers","year":"2021","journal-title":"Nat. Rev. Cancer"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.drup.2018.03.001","article-title":"How the Warburg effect supports aggressiveness and drug resistance of cancer cells?","volume":"38","author":"Icard","year":"2018","journal-title":"Drug Resist. Updates"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1001\/jama.2018.19323","article-title":"Breast cancer treatment: A review","volume":"321","author":"Waks","year":"2019","journal-title":"JAMA"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Pucci, C., Martinelli, C., and Ciofani, G. (2019). Innovative approaches for cancer treatment: Current perspectives and new challenges. Ecancermedicalscience, 13.","DOI":"10.3332\/ecancer.2019.961"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1016\/j.ucl.2012.07.008","article-title":"Targeted therapies in metastatic castration-resistant prostate cancer: Beyond the androgen receptor","volume":"39","author":"Loriot","year":"2012","journal-title":"Urol. Clin."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1016\/S1470-2045(05)70424-1","article-title":"Selection of adjuvant chemotherapy for treatment of node-positive breast cancer","volume":"6","author":"Trudeau","year":"2005","journal-title":"Lancet Oncol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1080\/02841860151116204","article-title":"What is cancer chemotherapy?","volume":"40","author":"Nygren","year":"2001","journal-title":"Acta Oncol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"v181","DOI":"10.1093\/annonc\/mdj978","article-title":"Challenges for chemotherapy in ovarian cancer","volume":"17","author":"Ozols","year":"2006","journal-title":"Ann. Oncol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1038\/nrclinonc.2015.120","article-title":"Opportunities and challenges of radiotherapy for treating cancer","volume":"12","author":"Schaue","year":"2015","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_13","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_14","unstructured":"Rosenblatt, E., and Zubizarreta, E. (2017). Radiotherapy in Cancer Care: Facing the Global Challenge, International Atomic Energy Agency Vienna."},{"key":"ref_15","first-page":"83","article-title":"Challenges of making radiotherapy accessible in developing countries","volume":"2013","author":"Samiei","year":"2013","journal-title":"Cancer Control"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"90","DOI":"10.2174\/2211738510666220210105113","article-title":"Theranostic applications of stimulusresponsive systems based on Fe2O3","volume":"10","author":"Pourmadadi","year":"2022","journal-title":"Pharm. Nanotechnol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Ahmad, I., Khan, M.F.A., Rahdar, A., Hussain, S., Tareen, F.K., Salim, M.W., Ajalli, N., Amirzada, M.I., and Khan, A. (2022). Design and Evaluation of pH Sensitive PEG-Protamine Nanocomplex of Doxorubicin for Treatment of Breast Cancer. Polymers, 14.","DOI":"10.3390\/polym14122403"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e202201271","DOI":"10.1002\/slct.202201271","article-title":"Nanotechnology for Therapy of Zoonotic Diseases: A Comprehensive Overview","volume":"7","author":"Arshad","year":"2022","journal-title":"ChemistrySelect"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Al-Joufi, F.A., Setia, A., Salem-Bekhit, M.M., Sahu, R.K., Alqahtani, F.Y., Widyowati, R., and Aleanizy, F.S. (2022). Molecular pathogenesis of colorectal cancer with an emphasis on recent advances in biomarkers, as well as nanotechnology-based diagnostic and therapeutic approaches. Nanomaterials, 12.","DOI":"10.3390\/nano12010169"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Alshareeda, A.T., Khatijah, M.N., and Al-Sowayan, B.S. (2022). Nanotechnology: A revolutionary approach to prevent breast cancer recurrence. Asian J. Surg.","DOI":"10.1016\/j.asjsur.2022.03.002"},{"key":"ref_21","first-page":"237","article-title":"Using Nanotechnology for Diagnosis and Treatment of Breast Cancer: A Review","volume":"84","author":"Wang","year":"2022","journal-title":"Indian J. Pharm. Sci."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Yadav, N., Dahiya, T., Chhillar, A.K., Rana, J.S., and Saini, H.M. (2022). Nanotechnology in Cancer Diagnostics and Therapeutics: A Review. Curr. Pharm. Biotechnol.","DOI":"10.2174\/1389201023666211222165508"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"217","DOI":"10.4103\/2278-344X.107832","article-title":"Polymeric nanoparticles for drug delivery and targeting: A comprehensive review","volume":"1","author":"Jawahar","year":"2012","journal-title":"Int. J. Health Allied Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"649","DOI":"10.2174\/1389200221666200508074348","article-title":"Polymeric nanoparticles for brain drug delivery\u2014A review","volume":"21","author":"Raman","year":"2020","journal-title":"Curr. Drug Metab."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Leyva-G\u00f3mez, G., Pi\u00f1\u00f3n-Segundo, E., Mendoza-Mu\u00f1oz, N., Zambrano-Zaragoza, M.L., Mendoza-Elvira, S., and Quintanar-Guerrero, D. (2018). Approaches in polymeric nanoparticles for vaginal drug delivery: A review of the state of the art. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19061549"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.colsurfb.2009.09.001","article-title":"Biodegradable polymeric nanoparticles based drug delivery systems","volume":"75","author":"Kumari","year":"2010","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_27","first-page":"16","article-title":"Different techniques for preparation of polymeric nanoparticles-a review","volume":"5","author":"Nagavarma","year":"2012","journal-title":"Asian J. Pharm. Clin. Res."},{"key":"ref_28","first-page":"38","article-title":"Polymeric nanoparticles: Review of synthesis methods and applications in drug delivery","volume":"1","author":"Jahangiri","year":"2018","journal-title":"J. Adv. Chem. Pharm. Mater. JACPM"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1016\/j.ijbiomac.2019.02.060","article-title":"Chitosan nanopolymers: An overview of drug delivery against cancer","volume":"130","author":"Shanmuganathan","year":"2019","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"116403","DOI":"10.1016\/j.carbpol.2020.116403","article-title":"Chitosan: A compound for drug delivery system in gastric cancer\u2014A review","volume":"242","author":"Shafabakhsh","year":"2020","journal-title":"Carbohydr. Polym."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Babu, A., and Ramesh, R. (2017). Multifaceted applications of chitosan in cancer drug delivery and therapy. Mar. Drugs, 15.","DOI":"10.3390\/md15040096"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1007\/s12033-014-9816-3","article-title":"Application of chitosan-based nanocarriers in tumor-targeted drug delivery","volume":"57","author":"Anarjan","year":"2015","journal-title":"Mol. Biotechnol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1016\/j.ijbiomac.2014.10.052","article-title":"Chitosan-based nanoparticles for tumor-targeted drug delivery","volume":"72","author":"Prabaharan","year":"2015","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"5985","DOI":"10.1016\/j.cell.2021.10.024","article-title":"A single-cell atlas of chromatin accessibility in the human genome","volume":"184","author":"Zhang","year":"2021","journal-title":"Cell"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"118464","DOI":"10.1016\/j.carbpol.2021.118464","article-title":"Chitosan-based nanodelivery systems for cancer therapy: Recent advances","volume":"272","author":"Narmani","year":"2021","journal-title":"Carbohydr. Polym."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1080\/00914037.2020.1869737","article-title":"Progress in nanomedicine-based drug delivery in designing of chitosan nanoparticles for cancer therapy","volume":"71","author":"Ahmad","year":"2022","journal-title":"Int. J. Polym. Mater. Polym. Biomater."},{"key":"ref_37","unstructured":"Manzoor, S., Ashraf, M.W., Tayyaba, S., and Hossain, M.K. (2021). Recent progress of fabrication, characterization, and applications of anodic aluminum oxide (AAO) membrane: A review. arXiv."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.1049\/mnl.2018.5070","article-title":"Biomedical applications of aluminium oxide nanoparticles","volume":"13","author":"Hassanpour","year":"2018","journal-title":"Micro Nano Lett."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.trac.2012.11.007","article-title":"Nanoporous anodic aluminum oxide for chemical sensing and biosensors","volume":"44","author":"Santos","year":"2013","journal-title":"TrAC Trends Anal. Chem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1016\/j.biotechadv.2011.08.005","article-title":"Where bio meets nano: The many uses for nanoporous aluminum oxide in biotechnology","volume":"30","author":"Ingham","year":"2012","journal-title":"Biotechnol. Adv."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"101755","DOI":"10.1016\/j.tice.2022.101755","article-title":"The therapeutic potential of \u03b3-Al2O3 nanoparticle containing 5-fluorouracil in the treatment of colorectal cancer","volume":"76","author":"Fasihi","year":"2022","journal-title":"Tissue Cell"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1615\/JLongTermEffMedImplants.2018025635","article-title":"Alumina biocompatibility","volume":"28","author":"Denes","year":"2018","journal-title":"J. Long Term Eff. Med. Implant."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"14460","DOI":"10.1021\/am503744z","article-title":"\u03b3-alumina modification with long chain carboxylic acid surface nanocrystals for biocompatible polysulfone nanocomposites","volume":"6","author":"Anaya","year":"2014","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1179\/174328408X287682","article-title":"Biocompatible alumina ceramic for total hip replacements","volume":"24","author":"Zeng","year":"2008","journal-title":"Mater. Sci. Technol."},{"key":"ref_45","unstructured":"Arbex, R., Rezende, L., Ambrosio, F., Costa, L., and Lombello, C. (2020, January 26\u201330). Cytotoxicity of Alumina and Calcium Hexaluminate: Test Conditions. Proceedings of the XXVII Brazilian Congress on Biomedical Engineering, CBEB 2020, Vit\u00f3ria, Brazil."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"4215","DOI":"10.1016\/j.ceramint.2019.10.140","article-title":"Synthesis and characterization of corrosion-resistant and biocompatible Al2O3\u2013TiB2 nanocomposite films on pure titanium","volume":"46","author":"Alvar","year":"2020","journal-title":"Ceram. Int."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"18247","DOI":"10.1016\/j.ceramint.2016.08.148","article-title":"Effects of carbon doping on the microstructural, micro\/nano-mechanical, and mesenchymal stromal cells biocompatibility and osteogenic differentiation properties of alumina","volume":"42","author":"Krishnamurithy","year":"2016","journal-title":"Ceram. Int."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"23","DOI":"10.11113\/mjfas.v15n2019.1224","article-title":"Preparation and characterization of superparamagnetic magnetite (Fe3O4) nanoparticles: A short review","volume":"15","author":"Koo","year":"2019","journal-title":"Malays. J. Fundam. Appl. Sci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2287","DOI":"10.1016\/j.arabjc.2018.04.013","article-title":"Green biosynthesis of superparamagnetic magnetite Fe3O4 nanoparticles and biomedical applications in targeted anticancer drug delivery system: A review","volume":"13","author":"Yew","year":"2020","journal-title":"Arab. J. Chem."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Anghelache, M., Turtoi, M., Petrovici, A.R., Fifere, A., Pinteala, M., and Calin, M. (2021). Development of dextran-coated magnetic nanoparticles loaded with protocatechuic acid for vascular inflammation therapy. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13091414"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2183","DOI":"10.1016\/j.biomaterials.2010.11.040","article-title":"Polyethylene glycol modified, cross-linked starch-coated iron oxide nanoparticles for enhanced magnetic tumor targeting","volume":"32","author":"Cole","year":"2011","journal-title":"Biomaterials"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Mannu, R., Karthikeyan, V., Velu, N., Arumugam, C., Roy, V.A., Gopalan, A.-I., Saianand, G., Sonar, P., Lee, K.-P., and Kim, W.-J. (2021). Polyethylene glycol coated magnetic nanoparticles: Hybrid nanofluid formulation, properties and drug delivery prospects. Nanomaterials, 11.","DOI":"10.3390\/nano11020440"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1238","DOI":"10.1002\/sia.4929","article-title":"Preparation and characterization of polyvinyl alcohol-grafted Fe3O4 magnetic nanoparticles through glutaraldehyde","volume":"44","author":"Kim","year":"2012","journal-title":"Surf. Interface Anal."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1186\/s13065-015-0125-0","article-title":"Sandal reactive dyes decolorization and cytotoxicity reduction using manganese peroxidase immobilized onto polyvinyl alcohol-alginate beads","volume":"9","author":"Bilal","year":"2015","journal-title":"Chem. Cent. J."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"3804","DOI":"10.1021\/acs.langmuir.1c03458","article-title":"In Vitro Study: Synthesis and Evaluation of Fe3O4\/CQD Magnetic\/Fluorescent Nanocomposites for Targeted Drug Delivery, MRI, and Cancer Cell Labeling Applications","volume":"38","author":"Nafchi","year":"2022","journal-title":"Langmuir"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"4973","DOI":"10.2147\/IJN.S35140","article-title":"Biocompatibility of magnetic Fe3O4 nanoparticles and their cytotoxic effect on MCF-7 cells","volume":"7","author":"Chen","year":"2012","journal-title":"Int. J. Nanomed."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"075102","DOI":"10.1088\/0957-4484\/21\/7\/075102","article-title":"Biocompatibility of Fe3O4 nanoparticles evaluated by in vitro cytotoxicity assays using normal, glia and breast cancer cells","volume":"21","author":"Ankamwar","year":"2010","journal-title":"Nanotechnology"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2805","DOI":"10.2147\/IJN.S24596","article-title":"Biocompatibility of Fe3O4@ Au composite magnetic nanoparticles in vitro and in vivo","volume":"6","author":"Li","year":"2011","journal-title":"Int. J. Nanomed."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"6110","DOI":"10.1166\/jnn.2010.2616","article-title":"On the biocompatibility of Fe3O4 ferromagnetic nanoparticles with human blood cells","volume":"10","author":"Stamopoulos","year":"2010","journal-title":"J. Nanosci. Nanotechnol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.fuproc.2013.08.020","article-title":"Study on the solubilization capacity of bio-oil in diesel by microemulsion technology with Span80 as surfactant","volume":"118","author":"Wang","year":"2014","journal-title":"Fuel Process. Technol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"313961","DOI":"10.1155\/2012\/313961","article-title":"5-Fluorouracil encapsulated chitosan nanoparticles for pH-stimulated drug delivery: Evaluation of controlled release kinetics","volume":"2012","author":"Pulat","year":"2012","journal-title":"J. Nanomater."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1016\/j.carbpol.2011.03.045","article-title":"Development of chitosan nanoparticles as drug delivery systems for 5-fluorouracil and leucovorin blends","volume":"85","author":"Li","year":"2011","journal-title":"Carbohydr. Polym."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"102155","DOI":"10.1016\/j.jddst.2020.102155","article-title":"5-Fluorouracil, innovative drug delivery systems to enhance bioavailability for topical use","volume":"61","author":"Amorim","year":"2021","journal-title":"J. Drug Deliv. Sci. Technol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.colsurfb.2013.07.042","article-title":"Potentiation of 5-fluorouracil encapsulated in zeolites as drug delivery systems for in vitro models of colorectal carcinoma","volume":"112","author":"Amorim","year":"2013","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1116","DOI":"10.1016\/j.ijbiomac.2018.02.143","article-title":"Sesbania gum based hydrogel as platform for sustained drug delivery: An \u2018in vitro\u2019study of 5-Fu release","volume":"113","author":"Pal","year":"2018","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"111","DOI":"10.4103\/2319-4170.130923","article-title":"Enhancing the anticancer effects of 5-fluorouracil: Current challenges and future perspectives","volume":"38","author":"Ghiringhelli","year":"2015","journal-title":"Biomed. J."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"111285","DOI":"10.1016\/j.biopha.2021.111285","article-title":"5-Fluorouracil (5-FU) resistance and the new strategy to enhance the sensitivity against cancer: Implication of DNA repair inhibition","volume":"137","author":"Sethy","year":"2021","journal-title":"Biomed. Pharmacother."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1016\/j.ijbiomac.2021.04.160","article-title":"Synthesis and characterization of chitosan\/polyvinylpyrrolidone coated nanoporous \u03b3-Alumina as a pH-sensitive carrier for controlled release of quercetin","volume":"183","author":"Nematollahi","year":"2021","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1016\/j.carbpol.2016.05.109","article-title":"Polyphenol-chitosan conjugates: Synthesis, characterization, and applications","volume":"151","author":"Hu","year":"2016","journal-title":"Carbohydr. Polym."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"4447","DOI":"10.1016\/j.matlet.2007.02.018","article-title":"Synthesis of magnetite (Fe3O4) nanoparticles without surfactants at room temperature","volume":"61","year":"2007","journal-title":"Mater. Lett."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"5324","DOI":"10.2174\/1381612821666150917094031","article-title":"Synthesis and applications of Fe3O4\/SiO2 core-shell materials","volume":"21","author":"Sonmez","year":"2015","journal-title":"Curr. Pharm. Des."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1552","DOI":"10.1016\/j.reactfunctpolym.2006.05.006","article-title":"In situ preparation of magnetic chitosan\/Fe3O4 composite nanoparticles in tiny pools of water-in-oil microemulsion","volume":"66","author":"Zhi","year":"2006","journal-title":"React. Funct. Polym."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"115882","DOI":"10.1016\/j.carbpol.2020.115882","article-title":"Facile preparation of polyacrylamide\/chitosan\/Fe3O4 composite hydrogels for effective removal of methylene blue from aqueous solution","volume":"234","author":"Zhang","year":"2020","journal-title":"Carbohydr. Polym."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Wulandari, I.O., Mardila, V.T., Santjojo, D.D.H., and Sabarudin, A. (2018). Preparation and characterization of chitosan-coated Fe3O4 nanoparticles using ex-situ co-precipitation method and tripolyphosphate\/sulphate as dual crosslinkers. IOP Conference Series: Materials Science and Engineering, IOP Publishing.","DOI":"10.1088\/1757-899X\/299\/1\/012064"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1016\/j.jphotobiol.2018.06.014","article-title":"Synthesis and characterization of carboxymethyl chitosan\/Fe3O4 and MnFe2O4 nanocomposites hydrogels for loading and release of curcumin","volume":"185","author":"Naderi","year":"2018","journal-title":"J. Photochem. Photobiol. B Biol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1016\/j.ijbiomac.2021.09.023","article-title":"Ultra pH-sensitive nanocarrier based on Fe2O3\/chitosan\/montmorillonite for quercetin delivery","volume":"191","author":"Ahmadi","year":"2021","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1016\/j.ijbiomac.2017.07.101","article-title":"Curcumin-loaded chitosan\/carboxymethyl starch\/montmorillonite bio-nanocomposite for reduction of dental bacterial biofilm formation","volume":"105","author":"Jahanizadeh","year":"2017","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/S0378-5173(02)00172-2","article-title":"5-Fluorouracil encapsulated alginate beads for the treatment of breast cancer","volume":"242","author":"Sargon","year":"2002","journal-title":"Int. J. Pharm."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"742","DOI":"10.2174\/15672018113109990049","article-title":"Optimization of size and encapsulation efficiency of 5-FU loaded chitosan nanoparticles by response surface methodology","volume":"10","author":"Honary","year":"2013","journal-title":"Curr. Drug Deliv."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"109828","DOI":"10.1016\/j.msec.2019.109828","article-title":"\u201cIn vitro\u201d behaviour of aptamer-functionalized polymeric nanocapsules loaded with 5-fluorouracil for targeted therapy","volume":"103","author":"Cadinoiu","year":"2019","journal-title":"Mater. Sci. Eng. C"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1007\/s00289-021-03537-9","article-title":"Application of different mathematical models for further investigation of in vitro drug release mechanisms based on magnetic nano-composite","volume":"79","author":"Jafari","year":"2022","journal-title":"Polym. Bull."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"12152","DOI":"10.1039\/C5NR07773G","article-title":"Doxorubicin loaded dual pH-and thermo-responsive magnetic nanocarrier for combined magnetic hyperthermia and targeted controlled drug delivery applications","volume":"8","author":"Hervault","year":"2016","journal-title":"Nanoscale"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1016\/j.colsurfb.2016.03.073","article-title":"Nanoporous anodic titanium dioxide layers as potential drug delivery systems: Drug release kinetics and mechanism","volume":"143","author":"Jarosz","year":"2016","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"874","DOI":"10.1002\/jps.2600501018","article-title":"Rate of release of medicaments from ointment bases containing drugs in suspension","volume":"50","author":"Higuchi","year":"1961","journal-title":"J. Pharm. Sci."},{"key":"ref_85","unstructured":"Bruschi, M.L. (2015). Strategies to Modify the Drug Release from Pharmaceutical Systems, Woodhead Publishing."},{"key":"ref_86","first-page":"129","article-title":"Comparison of chemosensitivity tests: Clonogenic assay versus MTT assay","volume":"56","author":"Kawada","year":"2002","journal-title":"Acta Med. Okayama"},{"key":"ref_87","first-page":"432","article-title":"Dose-response modeling using MTT assay: A short review","volume":"11","author":"Nikzad","year":"2014","journal-title":"Life Sci. J."},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Sharma, N., Sharma, V., Jain, Y., Kumari, M., Gupta, R., Sharma, S., and Sachdev, K. (2017). Synthesis and characterization of graphene oxide (GO) and reduced graphene oxide (rGO) for gas sensing application. Macromolecular Symposia, Wiley Online Library.","DOI":"10.1002\/masy.201700006"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"141","DOI":"10.3390\/md13010141","article-title":"Does the use of chitosan contribute to oxalate kidney stone formation?","volume":"13","author":"Queiroz","year":"2014","journal-title":"Mar. Drugs"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"20224","DOI":"10.1021\/acsomega.0c01903","article-title":"Extraction, characterization, and antimicrobial activity of chitosan from horse mussel modiolus modiolus","volume":"5","author":"Varma","year":"2020","journal-title":"ACS Omega"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1007\/s10924-019-01407-0","article-title":"Modification of novel chitosan-starch cross-linked derivatives polymers: Synthesis and characterization","volume":"27","author":"Atangana","year":"2019","journal-title":"J. Polym. Environ."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1","DOI":"10.9734\/IRJPAC\/2016\/23315","article-title":"Chromium (VI) ions removal from tannery effluent using chitosan-microcrystalline cellulose composite as adsorbent","volume":"10","author":"Yasmeen","year":"2016","journal-title":"Int. Res. J. Pure Appl. Chem."},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Abdel-Naby, A.S., Nabil, S., Aldulaijan, S., Ababutain, I.M., Alghamdi, A.I., Almubayedh, S., and Khalil, K.D. (2021). Synthesis, Characterization of Chitosan-Aluminum Oxide Nanocomposite for Green Synthesis of Annulated Imidazopyrazol Thione Derivatives. Polymers, 13.","DOI":"10.3390\/polym13071160"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1016\/j.ijbiomac.2021.01.067","article-title":"Preparation of pH-sensitive chitosan\/polyvinylpyrrolidone\/\u03b1-Fe2O3 nanocomposite for drug delivery application: Emphasis on ameliorating restrictions","volume":"173","author":"Gerami","year":"2021","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"409","DOI":"10.3390\/ijms13010409","article-title":"In vitro antioxidant, anticoagulant and antimicrobial activity and in inhibition of cancer cell proliferation by xylan extracted from corn cobs","volume":"13","author":"Fidelis","year":"2011","journal-title":"Int. J. Mol. Sci."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/j.msec.2017.05.126","article-title":"Peptide functionalized poly ethylene glycol-poly caprolactone nanomicelles for specific cabazitaxel delivery to metastatic breast cancer cells","volume":"80","author":"Mahdaviani","year":"2017","journal-title":"Mater. Sci. Eng. C"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1016\/j.ijbiomac.2019.01.191","article-title":"Preparation of pH-sensitive Fe3O4@ C\/carboxymethyl cellulose\/chitosan composite beads for diclofenac sodium delivery","volume":"127","author":"Sun","year":"2019","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_98","first-page":"28","article-title":"New sol-gel derived aluminum oxide-ibuprofen nanocomposite as a controlled releasing medication","volume":"2","author":"Tarlani","year":"2017","journal-title":"Nanomed. Res. J."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1007\/s11368-012-0506-0","article-title":"Dechlorinating transformation of propachlor through nucleophilic substitution by dithionite on the surface of alumina","volume":"12","author":"Liu","year":"2012","journal-title":"J. Soils Sediments"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"8347","DOI":"10.1007\/s10854-018-8845-2","article-title":"Green synthesis of amorphous and gamma aluminum oxide nanoparticles by tragacanth gel and comparison of their photocatalytic activity for the degradation of organic dyes","volume":"29","author":"Atrak","year":"2018","journal-title":"J. Mater. Sci. Mater. Electron."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1492","DOI":"10.1021\/la00030a012","article-title":"Surface sites on spinel-type and corundum-type metal oxide powders","volume":"9","author":"Busca","year":"1993","journal-title":"Langmuir"},{"key":"ref_102","first-page":"1015","article-title":"Design and fabrication of ordered mesoporous alumina scaffold for drug delivery of poorly water soluble drug","volume":"2","author":"Borbane","year":"2015","journal-title":"Austin Ther."},{"key":"ref_103","first-page":"1","article-title":"FTIR and X-ray diffraction analysis of Al2O3 nanostructured thin film prepared at low temperature using spray pyrolysis method","volume":"11","author":"Naayi","year":"2018","journal-title":"Int. J. Nanoelectron. Mater."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.apcata.2011.07.024","article-title":"Catalytic conversion of alcohols over alumina\u2013zirconia mixed oxides: Reactivity and selectivity","volume":"404","author":"Dabbagh","year":"2011","journal-title":"Appl. Catal. A Gen."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1445","DOI":"10.1016\/j.jhazmat.2010.12.034","article-title":"Synthesis and physicochemical characterizations of nanostructured Pt\/Al2O3\u2013CeO2 catalysts for total oxidation of VOCs","volume":"186","author":"Abbasi","year":"2011","journal-title":"J. Hazard. Mater."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1177\/0263617416674216","article-title":"Effective and selective removal of aromatic amines from water by Cu2+-treated chitosan\/alumina nanocomposite","volume":"35","author":"Zavareh","year":"2017","journal-title":"Adsorpt. Sci. Technol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.phpro.2013.10.014","article-title":"Synthesis and characterization of biodegradable ultrasonicated films made from chitosan\/Al2O3 polymer nanocomposites","volume":"49","author":"Prakash","year":"2013","journal-title":"Phys. Procedia"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1016\/j.ijbiomac.2016.09.015","article-title":"Removal of nitrate and phosphate using chitosan\/Al2O3\/Fe3O4 composite nanofibrous adsorbent: Comparison with chitosan\/Al2O3\/Fe3O4 beads","volume":"93","author":"Bozorgpour","year":"2016","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1016\/j.jmmm.2014.12.054","article-title":"Solvothermal synthesis and characterization of monodisperse superparamagnetic iron oxide nanoparticles","volume":"379","author":"Li","year":"2015","journal-title":"J. Magn. Magn. Mater."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.cej.2013.04.060","article-title":"Thiol modified Fe3O4@ SiO2 as a robust, high effective, and recycling magnetic sorbent for mercury removal","volume":"226","author":"Zhang","year":"2013","journal-title":"Chem. Eng. J."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"045010","DOI":"10.1088\/2043-6262\/7\/4\/045010","article-title":"Synthesis and characterization of chitosan-coated magnetite nanoparticles and their application in curcumin drug delivery","volume":"7","author":"Pham","year":"2016","journal-title":"Adv. Nat. Sci. Nanosci. Nanotechnol."},{"key":"ref_112","first-page":"300","article-title":"Effects of shell-thickness on the powder morphology, magnetic behavior and stability of the chitosan-coated Fe3O4 nanoparticles","volume":"61","author":"Isasi","year":"2021","journal-title":"Bolet\u00edn Soc. Espa\u00f1ola Cer\u00e1mica Vidr."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"1024","DOI":"10.1039\/C4RA11615A","article-title":"An in vitro cytotoxicity study of 5-fluorouracil encapsulated chitosan\/gold nanocomposites towards MCF-7 cells","volume":"5","author":"Nivethaa","year":"2015","journal-title":"RSC Adv."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"690918","DOI":"10.1155\/2013\/690918","article-title":"The effect of Ag content of the chitosan-silver nanoparticle composite material on the structure and antibacterial activity","volume":"2013","author":"Akmaz","year":"2013","journal-title":"Adv. Mater. Sci. Eng."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"12179","DOI":"10.1039\/C8RA00510A","article-title":"Eco-friendly synthesis of graphene\u2013chitosan composite hydrogel as efficient adsorbent for Congo red","volume":"8","author":"Omidi","year":"2018","journal-title":"RSC Adv."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"5775","DOI":"10.3390\/s8095775","article-title":"Use of Fe3O4 nanoparticles for enhancement of biosensor response to the herbicide 2, 4-dichlorophenoxyacetic acid","volume":"8","author":"Loh","year":"2008","journal-title":"Sensors"},{"key":"ref_117","doi-asserted-by":"crossref","unstructured":"Dai, L., Jin, Z., Liu, X., Feng, L., Ma, J., and Ling, Z. (2021). Green Synthesis of Carbon-Encapsulated Magnetic Fe3O4 Nanoparticles Using Hydrothermal Carbonization from Rattan Holocelluloses. Coatings, 11.","DOI":"10.3390\/coatings11111397"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1039\/D0RA08230A","article-title":"Facile synthesis of superparamagnetic Fe3O4@ noble metal core\u2013shell nanoparticles by thermal decomposition and hydrothermal methods: Comparative study and catalytic applications","volume":"11","author":"Bakr","year":"2021","journal-title":"RSC Adv."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1016\/j.jsps.2014.11.010","article-title":"Formulation and characterization of 5-Fluorouracil enteric coated nanoparticles for sustained and localized release in treating colorectal cancer","volume":"23","author":"Tummala","year":"2015","journal-title":"Saudi Pharm. J."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"15","DOI":"10.24193\/subbphys.2017.02","article-title":"XRD checking of crystalline forms resulted by slow evaporation of 5-fluorouracil solutions obtained with different solvents","volume":"62","author":"Simon","year":"2017","journal-title":"Studia Univ. Babes Bolyai Phys."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"12288","DOI":"10.1038\/s41598-019-48180-7","article-title":"Bio-mediated synthesis of 5-FU based nanoparticles employing orange fruit juice: A novel drug delivery system to treat skin fibrosarcoma in model animals","volume":"9","author":"Mohammad","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.ijbiomac.2021.03.146","article-title":"Ameliorating quercetin constraints in cancer therapy with pH-responsive agarose-polyvinylpyrrolidone-hydroxyapatite nanocomposite encapsulated in double nanoemulsion","volume":"182","author":"Samadi","year":"2021","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"3177","DOI":"10.1039\/C6NJ04107H","article-title":"Dendritic chitosan as a magnetic and biocompatible nanocarrier for the simultaneous delivery of doxorubicin and methotrexate to MCF-7 cell line","volume":"41","author":"Rahimi","year":"2017","journal-title":"New J. Chem."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.jconrel.2019.02.030","article-title":"Measuring particle size distribution of nanoparticle enabled medicinal products, the joint view of EUNCL and NCI-NCL. A step by step approach combining orthogonal measurements with increasing complexity","volume":"299","author":"Caputo","year":"2019","journal-title":"J. Control. Release"},{"key":"ref_125","first-page":"265","article-title":"Effect of zeta potential on the properties of nano-drug delivery systems-a review (Part 2)","volume":"12","author":"Honary","year":"2013","journal-title":"Trop. J. Pharm. Res."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"1422","DOI":"10.1016\/j.ijbiomac.2020.09.166","article-title":"Chitosan\/carbon quantum dot\/aptamer complex as a potential anticancer drug delivery system towards the release of 5-fluorouracil","volume":"165","author":"Zavareh","year":"2020","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"8487","DOI":"10.2147\/IJN.S170723","article-title":"Potential adverse effects of nanoparticles on the reproductive system","volume":"13","author":"Wang","year":"2018","journal-title":"Int. J. Nanomed."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1016\/j.ijbiomac.2021.06.184","article-title":"The synthesis and characterization of targeted delivery curcumin using chitosan-magnetite-reduced graphene oxide as nano-carrier","volume":"186","author":"Kazemi","year":"2021","journal-title":"Int. J. Biol. Macromol."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/27\/17\/5369\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:14:04Z","timestamp":1760141644000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/27\/17\/5369"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,23]]},"references-count":128,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2022,9]]}},"alternative-id":["molecules27175369"],"URL":"https:\/\/doi.org\/10.3390\/molecules27175369","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,23]]}}}