{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T16:25:36Z","timestamp":1777479936657,"version":"3.51.4"},"reference-count":54,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,10,2]],"date-time":"2025-10-02T00:00:00Z","timestamp":1759363200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Iuliu Ha\u021bieganu University of Cluj-Napoca"}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background: Hepatocellular carcinoma is associated with high mortality and increasing incidence. Sorafenib, a cornerstone of therapy for advanced hepatocellular carcinoma, presents certain disadvantages, including low bioavailability and poor water solubility. This work describes a new strategy for sorafenib-targeted delivery aimed at improving treatment efficiency and reducing side effects. Methods: Magnetic nanoparticles coated with azelaic acid were modified with aptamer molecules that specifically recognize human liver cancer cell line HepG2, ensuring specificity for the tumor tissue. The nanoparticles were further loaded with sorafenib. The obtained drug delivery system was extensively characterized using UV-Vis spectrophotometry, transmission electron microscopy, X-ray diffraction, Fourier-transform infrared spectroscopy, X-ray photoelectron spectroscopy, and electrochemical impedance spectroscopy. Results: The drug delivery system demonstrated a higher release of sorafenib at acidic pH compared to pH 7.4. The cell internalization of the bare and aptamer-modified magnetic nanoparticles was assessed in HepG2 and human normal foreskin fibroblasts BJ cell lines, demonstrating that the aptamer significantly enhances internalization in tumor cells, while having no impact on healthy cells. Conclusions: The sorafenib-modified nanoparticles exhibited excellent cytocompatibility with BJ cells across all tested concentrations, while showing cytotoxicity towards HepG2 cells at higher concentrations, confirming the selectivity of the system.<\/jats:p>","DOI":"10.3390\/pharmaceutics17101292","type":"journal-article","created":{"date-parts":[[2025,10,2]],"date-time":"2025-10-02T15:07:48Z","timestamp":1759417668000},"page":"1292","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Aptamer-Modified Magnetic Nanoparticles as Targeted Drug Delivery Systems for Hepatocellular Carcinoma"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7789-6798","authenticated-orcid":false,"given":"Alexandra","family":"Pusta","sequence":"first","affiliation":[{"name":"Department of Analytical Chemistry and Instrumental Analysis, Iuliu Ha\u021bieganu University of Medicine and Pharmacy, 4 Pasteur Street, 400349 Cluj-Napoca, Romania"},{"name":"Department of Medical Devices, Iuliu Ha\u021bieganu University of Medicine and Pharmacy, 4 Pasteur Street, 400349 Cluj-Napoca, Romania"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2572-6724","authenticated-orcid":false,"given":"Mihaela","family":"Tertis","sequence":"additional","affiliation":[{"name":"Department of Analytical Chemistry and Instrumental Analysis, Iuliu Ha\u021bieganu University of Medicine and Pharmacy, 4 Pasteur Street, 400349 Cluj-Napoca, Romania"}]},{"given":"Bianca","family":"Ciocan","sequence":"additional","affiliation":[{"name":"Department of Analytical Chemistry and Instrumental Analysis, Iuliu Ha\u021bieganu University of Medicine and Pharmacy, 4 Pasteur Street, 400349 Cluj-Napoca, Romania"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6355-8381","authenticated-orcid":false,"given":"Rodica","family":"Turcu","sequence":"additional","affiliation":[{"name":"National Institute for Research and Development of Isotopic and Molecular Technologies, 67\u2013103 Donat Street, 400293 Cluj-Napoca, Romania"}]},{"given":"Izabell","family":"Cr\u0103ciunescu","sequence":"additional","affiliation":[{"name":"National Institute for Research and Development of Isotopic and Molecular Technologies, 67\u2013103 Donat Street, 400293 Cluj-Napoca, Romania"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0719-8016","authenticated-orcid":false,"given":"Victor C.","family":"Diculescu","sequence":"additional","affiliation":[{"name":"National Institute of Materials Physics, 405A Atomi\u015ftilor Street, 077125 M\u0103gurele, Romania"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0289-8988","authenticated-orcid":false,"given":"George E.","family":"Stan","sequence":"additional","affiliation":[{"name":"National Institute of Materials Physics, 405A Atomi\u015ftilor Street, 077125 M\u0103gurele, Romania"}]},{"given":"Stefan","family":"Bulat","sequence":"additional","affiliation":[{"name":"National Institute of Materials Physics, 405A Atomi\u015ftilor Street, 077125 M\u0103gurele, Romania"}]},{"given":"Alina","family":"Porfire","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology and Biopharmaceutics, Iuliu Ha\u021bieganu University of Medicine and Pharmacy, 41 Victor Babe\u015f Street, 400012 Cluj-Napoca, Romania"}]},{"given":"Andreea-Elena","family":"Petru","sequence":"additional","affiliation":[{"name":"Department of Toxicology, Faculty of Pharmacy, Iuliu Ha\u021bieganu University of Medicine and Pharmacy, 8 Victor Babe\u015f, Street, 400012 Cluj-Napoca, Romania"}]},{"given":"Ionel","family":"Fize\u0219an","sequence":"additional","affiliation":[{"name":"Department of Toxicology, Faculty of Pharmacy, Iuliu Ha\u021bieganu University of Medicine and Pharmacy, 8 Victor Babe\u015f, Street, 400012 Cluj-Napoca, Romania"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6318-3826","authenticated-orcid":false,"given":"Simona","family":"Mirel","sequence":"additional","affiliation":[{"name":"Department of Medical Devices, Iuliu Ha\u021bieganu University of Medicine and Pharmacy, 4 Pasteur Street, 400349 Cluj-Napoca, Romania"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4158-3324","authenticated-orcid":false,"given":"Cecilia","family":"Cristea","sequence":"additional","affiliation":[{"name":"Department of Analytical Chemistry and Instrumental Analysis, Iuliu Ha\u021bieganu University of Medicine and Pharmacy, 4 Pasteur Street, 400349 Cluj-Napoca, Romania"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1038\/s41572-020-00240-3","article-title":"Hepatocellular carcinoma","volume":"7","author":"Llovet","year":"2021","journal-title":"Nat. Rev. Dis. Prim."},{"key":"ref_2","first-page":"229","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. Clin."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1038\/s41575-020-00395-0","article-title":"Locoregional therapies in the era of molecular and immune treatments for hepatocellular carcinoma","volume":"18","author":"Llovet","year":"2021","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_4","first-page":"13","article-title":"Dissolution enhancement of sorafenib tosylate by co-milling with tetradecanol post-extracted using supercritical carbon dioxide","volume":"75","author":"Choi","year":"2020","journal-title":"Pharmazie"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1038\/s41392-020-0187-x","article-title":"The mechanisms of sorafenib resistance in hepatocellular carcinoma: Theoretical basis and therapeutic aspects","volume":"5","author":"Tang","year":"2020","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1515\/ntrev-2022-0058","article-title":"Formulation of polymeric nanoparticles loaded sorafenib; Evaluation of cytotoxicity, molecular evaluation, and gene expression studies in lung and breast cancer cell lines","volume":"11","author":"Abdellatif","year":"2022","journal-title":"Nanotechnol. Rev."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1469","DOI":"10.2147\/IJN.S237335","article-title":"Sorafenib-loaded nanoparticles based on biodegradable dendritic polymers for enhanced therapy of hepatocellular carcinoma","volume":"15","author":"Li","year":"2020","journal-title":"Int. J. Nanomedicine"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Bartos, A., Iancu, I., Ciobanu, L., Onaciu, A., Moldovan, C., Moldovan, A., Moldovan, R.C., Tigu, A.B., Stiufiuc, G.F., and Toma, V. (2022). Hybrid Lipid Nanoformulations for Hepatoma Therapy: Sorafenib Loaded Nanoliposomes-A Preliminary Study. Nanomaterials, 12.","DOI":"10.3390\/nano12162833"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"5464","DOI":"10.7150\/thno.54822","article-title":"Current status of sorafenib nanoparticle delivery systems in the treatment of hepatocellular carcinoma","volume":"11","author":"Kong","year":"2021","journal-title":"Theranostics"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2007","DOI":"10.1080\/10717544.2018.1531953","article-title":"Low-density lipoprotein decorated silica nanoparticles co-delivering sorafenib and doxorubicin for effective treatment of hepatocellular carcinoma","volume":"25","author":"Ye","year":"2018","journal-title":"Drug Deliv."},{"key":"ref_11","first-page":"492","article-title":"Co-delivery of sorafenib and siVEGF based on mesoporous silica nanoparticles for ASGPR mediated targeted HCC therapy","volume":"111","author":"Zheng","year":"2018","journal-title":"Eur. J. Pharm. Sci. Off. J. Eur. Fed. Pharm. Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"8445","DOI":"10.2147\/IJN.S223920","article-title":"Design And Characterisation Of Novel Sorafenib-Loaded Carbon Nanotubes With Distinct Tumour-Suppressive Activity In Hepatocellular Carcinoma","volume":"14","author":"Elsayed","year":"2019","journal-title":"Int. J. Nanomed."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jphotobiol.2018.11.013","article-title":"Biosynthesis of sorafenib coated graphene nanosheets for the treatment of gastric cancer in patients in nursing care","volume":"191","author":"Xu","year":"2019","journal-title":"J. Photochem. Photobiol. B."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/j.jcis.2021.09.174","article-title":"Magnetic implants in vivo guiding sorafenib liver delivery by superparamagnetic solid lipid nanoparticles","volume":"608","author":"Iacobazzi","year":"2022","journal-title":"J. Colloid Interface Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1049\/iet-nbt.2020.0139","article-title":"Magnetically responsive, sorafenib loaded alginate microspheres for hepatocellular carcinoma treatment","volume":"14","author":"Alpdemir","year":"2020","journal-title":"IET Nanobiotechnol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Dahiya, M., Awasthi, R., Yadav, J.P., Sharma, S., Dua, K., and Dureja, H. (2023). Chitosan based sorafenib tosylate loaded magnetic nanoparticles: Formulation and in-vitro characterization. Int. J. Biol. Macromol., 242.","DOI":"10.1016\/j.ijbiomac.2023.124919"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2431","DOI":"10.1007\/s12274-017-1444-3","article-title":"Sorafenib delivery nanoplatform based on superparamagnetic iron oxide nanoparticles magnetically targets hepatocellular carcinoma","volume":"10","author":"Depalo","year":"2017","journal-title":"Nano Res."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Ebadi, M., Buskaran, K., Bullo, S., Hussein, M.Z., Fakurazi, S., and Pastorin, G. (2020). Synthesis and cytotoxicity study of magnetite nanoparticles coated with polyethylene glycol and sorafenib\u2013zinc\/aluminium layered double hydroxide. Polymers, 12.","DOI":"10.3390\/polym12112716"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Ebadi, M., Bullo, S., Buskara, K., Hussein, M.Z., Fakurazi, S., and Pastorin, G. (2020). Release of a liver anticancer drug, sorafenib from its PVA\/LDH- and PEG\/LDH-coated iron oxide nanoparticles for drug delivery applications. Sci. Rep., 10.","DOI":"10.1038\/s41598-020-76504-5"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Ebadi, M., Rifqi Md Zain, A., Tengku Abdul Aziz, T.H., Mohammadi, H., Tee, C.A.T., and Rahimi Yusop, M. (2023). Formulation and Characterization of Fe3O4@PEG Nanoparticles Loaded Sorafenib; Molecular Studies and Evaluation of Cytotoxicity in Liver Cancer Cell Lines. Polymers, 15.","DOI":"10.3390\/polym15040971"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Pusta, A., Tertis, M., Cr\u0103ciunescu, I., Turcu, R., Mirel, S., and Cristea, C. (2023). Recent Advances in the Development of Drug Delivery Applications of Magnetic Nanomaterials. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15071872"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"100284","DOI":"10.1016\/j.apsadv.2022.100284","article-title":"Iron oxide nanoparticles and their pharmaceutical applications","volume":"11","author":"Attia","year":"2022","journal-title":"Appl. Surf. Sci. Adv."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"137994","DOI":"10.1016\/j.electacta.2021.137994","article-title":"Aptamers in biomedicine: Selection strategies and recent advances","volume":"376","author":"Hosu","year":"2021","journal-title":"Electrochim. Acta"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1038\/s43586-023-00238-7","article-title":"In vitro selection of aptamers and their applications","volume":"3","author":"DeRosa","year":"2023","journal-title":"Nat. Rev. Methods Prim."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1358","DOI":"10.1016\/j.apsb.2023.01.017","article-title":"Recent progress of aptamer\u2013drug conjugates in cancer therapy","volume":"13","author":"He","year":"2023","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.ejpb.2019.10.003","article-title":"Selective anti-ErbB3 aptamer modified sorafenib microparticles: In vitro and in vivo toxicity assessment","volume":"145","author":"Ali","year":"2019","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1080\/10717544.2022.2149897","article-title":"Aptamer-mediated hollow MnO(2) for targeting the delivery of sorafenib","volume":"30","author":"Wang","year":"2023","journal-title":"Drug Deliv."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"57362","DOI":"10.1021\/acsami.0c17660","article-title":"Co-delivery of Sorafenib and CRISPR\/Cas9 Based on Targeted Core\u2013Shell Hollow Mesoporous Organosilica Nanoparticles for Synergistic HCC Therapy","volume":"12","author":"Zhang","year":"2020","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1021\/ac701962v","article-title":"Identification of liver cancer-specific aptamers using whole live cells","volume":"80","author":"Shangguan","year":"2008","journal-title":"Anal. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"11132","DOI":"10.1021\/acs.jpcc.1c01053","article-title":"High-Performance Functionalized Magnetic Nanoparticles with Tailored Sizes and Shapes for Localized Hyperthermia Applications","volume":"125","author":"Palade","year":"2021","journal-title":"J. Phys. Chem. C"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Fizesan, I., Iacovita, C., Pop, A., Kiss, B., Dudric, R., Stiufiuc, R., Lucaciu, C.M., and Loghin, F. (2021). The Effect of Zn-Substitution on the Morphological, Magnetic, Cytotoxic, and In Vitro Hyperthermia Properties of Polyhedral Ferrite Magnetic Nanoparticles. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13122148"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.bios.2019.05.012","article-title":"Impedimetric aptasensor for the label-free and selective detection of Interleukin-6 for colorectal cancer screening","volume":"137","author":"Tertis","year":"2019","journal-title":"Biosens. Bioelectron."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"N\u00e9meth, Z., Cs\u00f3ka, I., Semnani Jazani, R., Sipos, B., Haspel, H., Kozma, G., K\u00f3nya, Z., and Dob\u00f3, D.G. (2022). Quality by Design-Driven Zeta Potential Optimisation Study of Liposomes with Charge Imparting Membrane Additives. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14091798"},{"key":"ref_34","first-page":"255","article-title":"Effect of zeta potential on the properties of nano-drug delivery systems\u2014A review (Part 1)","volume":"12","author":"Honary","year":"2013","journal-title":"Trop. J. Pharm. Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"104044","DOI":"10.1016\/j.jddst.2022.104044","article-title":"Sorafenib tosylate loaded superparamagnetic nanoparticles: Development, optimization and cytotoxicity analysis on HepG2 human hepatocellular carcinoma cell line","volume":"79","author":"Dahiya","year":"2023","journal-title":"J. Drug Deliv. Sci. Technol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1016\/j.aej.2020.09.061","article-title":"Drug delivery system based on magnetic iron oxide nanoparticles coated with (polyvinyl alcohol-zinc\/aluminium-layered double hydroxide-sorafenib)","volume":"60","author":"Ebadi","year":"2021","journal-title":"Alexandria Eng. J."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"155978","DOI":"10.1016\/j.cej.2024.155978","article-title":"Magnetic Fe3O4@MOF@aptamer-mediated entropy-driven fluorescence biosensor for multiplexed and DNA extraction- and amplification-free detection of pathogenic bacteria","volume":"499","author":"Lu","year":"2024","journal-title":"Chem. Eng. J."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2933","DOI":"10.1002\/jssc.201700103","article-title":"Aptamer-functionalized Fe3O4 magnetic nanoparticles as a solid-phase extraction adsorbent for the selective extraction of berberine from Cortex phellodendri","volume":"40","author":"Jiang","year":"2017","journal-title":"J. Sep. Sci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/0038-1098(72)91162-3","article-title":"Infrared absorption spectra and cation distributions in (Mn, Fe)3O4","volume":"11","author":"Ishii","year":"1972","journal-title":"Solid State Commun."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2493","DOI":"10.1016\/j.corsci.2008.06.034","article-title":"Quantitative analysis of iron oxides using Fourier transform infrared spectrophotometry","volume":"50","author":"Namduri","year":"2008","journal-title":"Corros. Sci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"455","DOI":"10.2174\/1573413712666151210230002","article-title":"Magnetic Nanoparticles in Medical Diagnostic Applications: Synthesis, Characterization and Proteins Conjugation","volume":"12","author":"Nalbandian","year":"2016","journal-title":"Curr. Nanosci."},{"key":"ref_42","first-page":"705","article-title":"Polymer-like and diamond-like carbon coatings prepared by RF-PECVD for biomedical applications","volume":"5","author":"Stan","year":"2010","journal-title":"Dig. J. Nanomater. Biostructures"},{"key":"ref_43","unstructured":"Mohrig, J.R.M., Hammond, C.N., and Schatz, P.F. (2006). Infrared spectroscopy. Techniques in Organic Chemistry, Freeman."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2436","DOI":"10.1039\/C8AY00386F","article-title":"Key factors in FTIR spectroscopic analysis of DNA: The sampling technique, pretreatment temperature and sample concentration","volume":"10","author":"Han","year":"2018","journal-title":"Anal. Methods"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Babi\u0107, S.D., and Serec, K. (2020). Sodium and manganese salt DNA thin films: An infrared spectroscopy study. Spectrochim. Acta Part A Mol. Biomol. Spectrosc., 241.","DOI":"10.1016\/j.saa.2020.118646"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"A25","DOI":"10.1021\/ed070pA25.5","article-title":"High Resolution XPS of Organic Polymers: The Scienta ESCA300 Database","volume":"70","author":"Beamson","year":"1993","journal-title":"J. Chem. Educ."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Malvindi, M.A., De Matteis, V., Galeone, A., Brunetti, V., Anyfantis, G.C., Athanassiou, A., Cingolani, R., and Pompa, P.P. (2014). Toxicity Assessment of Silica Coated Iron Oxide Nanoparticles and Biocompatibility Improvement by Surface Engineering. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0085835"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Predoi, D., Iconaru, S.L., Predoi, M.V., Buton, N., Megier, C., and Motelica-Heino, M. (2019). Biocompatible Layers Obtained from Functionalized Iron Oxide Nanoparticles in Suspension. Coatings, 9.","DOI":"10.3390\/coatings9120773"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Hanot, C.C., Choi, Y.S., Anani, T.B., Soundarrajan, D., and David, A.E. (2016). Effects of Iron-Oxide Nanoparticle Surface Chemistry on Uptake Kinetics and Cytotoxicity in CHO-K1 Cells. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17010054"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Meng, Y.Q., Shi, Y.N., Zhu, Y.P., Liu, Y.Q., Gu, L.W., Liu, D.D., Ma, A., Xia, F., Guo, Q.Y., and Xu, C.C. (2024). Recent trends in preparation and biomedical applications of iron oxide nanoparticles. J. Nanobiotechnol., 22.","DOI":"10.1186\/s12951-023-02235-0"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1038\/s41420-023-01490-2","article-title":"Recent progress in the effect of magnetic iron oxide nanoparticles on cells and extracellular vesicles","volume":"9","author":"Chen","year":"2023","journal-title":"Cell Death Discov."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"145103","DOI":"10.1088\/0957-4484\/21\/14\/145103","article-title":"Interactions between sub-10-nm iron and cerium oxide nanoparticles and 3T3 fibroblasts: The role of the coating and aggregation state","volume":"21","author":"Safi","year":"2010","journal-title":"Nanotechnology"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Iacovi\u021b\u0103, C., Fize\u0219an, I., Nitica, S., Florea, A., Barbu-Tudoran, L., Dudric, R., Pop, A., Vedeanu, N., Crisan, O., and Tetean, R. (2021). Silica Coating of Ferromagnetic Iron Oxide Magnetic Nanoparticles Significantly Enhances Their Hyperthermia Performances for Efficiently Inducing Cancer Cells Death In Vitro. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13122026"},{"key":"ref_54","first-page":"51","article-title":"Endocytosis and exocytosis of nanoparticles in mammalian cells","volume":"9","author":"Oh","year":"2014","journal-title":"Int. J. Nanomedicine"}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/17\/10\/1292\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,2]],"date-time":"2025-10-02T15:12:48Z","timestamp":1759417968000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/17\/10\/1292"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,2]]},"references-count":54,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2025,10]]}},"alternative-id":["pharmaceutics17101292"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics17101292","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,2]]}}}