FUNCTIONALIZED FE3O4 NANOCOMPOSITES AS PLATFORMS FOR BIOACTIVE MOLECULE IMMOBILIZATION AND TARGETED DRUG DELIVERY
DOI:
https://doi.org/10.32782/naturaljournal.17.2026.11Keywords:
magnetite, nanocomposites, surface functionalisation, drug immobilisation, targeted deliveryAbstract
This review summarises various modern approaches to the synthesis and functionalisation of magnetite (Fe3O4) magnetic nanoparticles and analyses their application as platforms for the immobilisation of biologically active molecules and pharmaceutical compounds. The main methods for producing Fe₃O₄ nanoparticles are discussed, in particular coprecipitation, hy drothermal, solvothermal and solgel synthesis, with an emphasis on their influence on the morphology, size and magnetic properties of the materials. Particular attention is paid to the surface functionalisation of nanoparticles via silanisation using APTES, MPTES and TEOS, which promotes the formation of active functional groups (–NH2, –SH, Si–OH) and determines the mechanisms of interaction with drug molecules. The main types of interactions are analysed, in particular electrostatic, hydrogen, covalent and coordination bonds, which determine the efficiency of immobilisation and the kinetics of drug release. Examples are given of the immobilisation of proteins, enzymes, immunoglobulins and anticancer drugs (doxorubicin, cisplatin) on the surface of magnetic nanocomposites. It is shown that the chemical nature of the surface determines not only the adsorption properties but also the biocompatibility, stability and therapeutic efficacy of the systems. The application of Fe3O4 nanoparticles in targeted drug delivery, magnetically controlled systems, hyperthermia and biosensors is considered separately. It is concluded that there is great potential for the creation of multifunctional nanocomposites with controllable surface properties for modern applications in nanomedicine.
References
Ahmad, S., Ni, H., Al-Mubaddel, F. S., Rizk, M. A., Ammar, M. B., Khan, A.U., Almarhoon, Z.M., Alanazi, A. A. & Zaki, M. E. (2025). Magnetic properties of different phases iron oxide nanoparticles prepared by micro emulsion-hydrothermal method. Scientific Reports, 15, 878. https://doi.org/10.1038/s41598-025-85145-5 [in English].
Azari, E., Niad, M., Nikmanesh, H. & Ahmadi, A. H. (2026). Fe3O4/SiO2 core-shell nanoparticles: dual-targeting drug carrier for doxorubicin delivery in cancer therapy. Results in Chemistry, 103181. https://doi.org/10.1016/j.rechem.2026.103181 [in English].
Chatterjee, Sh., Das, A., Datta, P., Thomas, S. & Ghosal, K. (2025). Medium molecular weight chitosan and magnetite based bead as a nanocomposite for delivery of anticancer drug: Development, evaluation and biocompatibility study. International Journal of Biological Macromolecules, 293, 139246. https://doi.org/10.1016/j.ijbiomac.2024.139246 [in English].
Das, A., Sengupta, P., Khanam, J., Augustine, R., Avnesh, S. Th., Thomas, S., Roy, S. & Ghosal, K. (2025). Magnetic nanoparticle as a new cutting-edge drug delivery and diagnostic platform: a review on its properties, synthesis, surface modification and applications. Carbohydrate Polymer Technologies and Applications, 11, 100905. https://doi.org/10.1016/j.carpta.2025.100905 [in English].
Gorbyk, P., Makhno, S., Lisova, O., Kusyak, A., Mazurenko, R., Prokopenko, S., Kusyak, N., Dubrovin, I., Turanska, S. & Petranovskaya, A. (2026). New Magnetosensitive Nanostructured Materials: Current Status and Research Prospects. Chemistry, Physics and Technology of Surface, 17(1), 37–49. https://doi.org/10.15407/hftp17.01.037 [in English].
Gu, L., Park, J.H., Duong, K.H., Ruoslahti, E. & Sailor, M.J. (2010). Magnetic luminescent porous silicon microparticles for localized delivery of molecular drug payloads. Small, 6(22), 2546–2552. https://doi.org/10.1002/smll.201000841 [in English].
Huang, J., Liu, C., Xiao, H., Wang, J., Jiang, D. & Gu, E. (2007). Zinc tetraaminophthalocyanine- Fe3O4 nanoparticle composite for laccase immobilization. International Journal of Nanomedicine, 2(4), 775–784. PMID: 18203444 [in English].
Izaz, S., Shah, A., Ahmad, W., Anwar, M., Shah, R., Khan, J. A., Noor, S. S., Abdulaziz, A. A. & Changseok, H. (2025). Synthesis, properties, and applications of Fe3O4 and Fe3O4-based nanocomposites. A review. Applied Catalysis Open, 203, 207049. https://doi.org/10.1016/
j.apcato.2025.207049 [in English].
Kohale, M., Inamdar, H., Kokate, K., Ingale, R., Joshi, J., Singh, D., Aavishkar, K., Polshettiwar, S., Aher, R. & Kulkarni, S. (2026). Engineering magnetite (Fe3O4) nanoparticles: Controlled synthesis, surface functionalization, and multidisciplinary technological applications: A Review, Progress in Crystal. Growth and Characterization of Materials, 72(1), 100698. https://doi.org/10.1016/j.pcrysgrow.2026.100698 [in English].
Kusiak, N. V., Kusyak, А. P., Svyrydiuk, K. P., Petranovska, A. L. & Gorbyk, P. P. (2021). Evaluation of the acid–base surface properties of nanoscale Fe3O4 and Fe3O4/SiO2 by potentiometric method. Molecular Crystals and Liquid Crystals, 719, 140–152. https://doi.org/10.1080/1542140 6.2021.1878744 [in English].
Lee, J. H. & Yeo, Y. (2015). Controlled Drug Release from Pharmaceutical Nanocarriers. Chemical Engineering Science, 125(24), 75–84. https://doi.org/10.1016/j.ces.2014.08.046 [in English].
Ma, Y., Manolache, S., Denes, F., Vail, D., Thamm, D. & Kurzman, I. (2006). Plasma synthesis of carbon-iron magnetic nanoparticles and immobilization of doxorubicin for targeted drug delivery. Journal of Materials Engineering and Performance, 15, 376–382. https://
doi.org/10.1361/105994906X113705 [in English].
Macková, H., Horák, D., Donchenko, G. V., Andriyaka, V. I., Palyvoda, O. M., Chernishov, V. I., Chekhun, V. F., Todor, I. N. & Kuzmenko, O. I. (2015). Colloidally stable surface-modified iron oxide nanoparticles: preparation, characterization and anti–tumor activity. Journal of Magnetism and Magnetic Materials, 380(15), 125–131. https://doi.org/10.1016/j.jmmm.2014.09.037 [in English].
Mishra, S. & Yadav, M. D. (2024). Magnetic Nanoparticles: A Comprehensive Review from Synthesis to Biomedical Frontiers. Langmuir, 40(33), 17239–17269. https://doi.org/10.1021/acs.langmuir.4c01532 [in English].
Mu, X., Tong, Z., Huang, Q., Liu, B., Liu, Z., Hao, L., Zhang, J., Gao, C., Wang, F. (2015). Nano-Magnetic Immunosensor Based on Staphylococcus Protein A and the Amplification Effect of HRP-Conjugated Phage Antibody. Sensors (Basel), 15(2), 3896–3910. https://doi.org/10.3390/s150203896 [in English].
Petranovska, A. L., Abramov, M. V., Opanashchuk, N. M., Turanska, S. P., Kusyak, N. V. & Gorbyk, P. P. (2018). Synthesis and properties of magnetically sensitive nanocomposites based on magnetite and gemcitabine. Chemistry, Physics and Technology of Surface, 9(4), 353–361. https://doi.org/10.15407/hftp09.04.353 [in English].
Petranovska, A. L., Abramov, M. V., Оpanashchuk, N. M., Turanska, S. P., Gorbyk, P. P., Kusyak, N. V., Kusyak, A. P., Lukyanova, N. Y. & Chekhun V. F. (2019). Magnetically sensitive nanocomposites and magnetic liquids based on magnetite, gemcitabine and antibody HER2. Chemistry, Physics and Technology of Surface, 10(4), 419–431. https://doi.org/10.15407/hftp10.04.419 [in English].
Popescu, R. C., Andronescu, E. & Vasile, B. S. (2019). Recent Advances in Magnetite Nanoparticle Functionalization for Nanomedicine. Nanomaterials, 9(12), 1791. https://doi.org/10.3390/nano9121791 [in English].
Qiu, J. D., Peng, H. P., Liang, R. P. & Xia, X. H. (2010). Facile preparation of magnetic core-shell Fe3O4@Au nanoparticle/myoglobin biofilm for direct electrochemistry. Biosens. Bioelectron, 25(6), 1447–1453. https://doi.org/10.1016/j.bios.2009.10.043 [in English].
Rarokar, N., Yadav, S., Saoji, S., Bramhe, P., Agade, R., Gurav, S., Khedekar, P., Subramaniyan, V., Wong, L.S. & Kumarasamy, V. (2024). Magnetic nanosystem a tool for targeted delivery and diagnostic application: Current challenges and recent advancement. International Journal of Pharmaceutics: X, 23(7), 100231. https://doi.org/10.1016/j.ijpx.2024.100231 [in English].
Rezaei, B., Yari, P., Sanders, S. M., Wang, H., Chugh, V. K., Liang, S., Mostufa, S., Xu, K., Wang, J.-P., Gómez-Pastora, J. & Wu, K. (2024). Magnetic Nanoparticles: A Review on Synthesis, Characterization, Functionalization, and Biomedical Applications. Small, 20, 2304848. https://doi.org/10.1002/smll.202304848 [in English].
Roy, K. & Roy, I. (2022). Therapeutic applications of magnetic nanoparticles: recent advances. Materials Advances, 3(20), 7425–7444. https://doi.org/10.1039/D2MA00444E [in English].
Shao, D., Xu, K., Song, X., Hu, J., Yang, W. & Wang, C. (2009). Effective adsorption and separation of lysozyme with PAA-modified Fe3O4@silica core/shell microspheres. Journal of Colloid and Interface Science, 336(2), 526–532. https://doi.org/10.1016/j.jcis.2009.02.061 [in English].
Trung, Th. B., Nguyen, V. S., Bashir, J. H., Mohammed, J. K., Kiat, J. H., Bach, P. Th., Minh, N. Q., Quyen, T. N., Hoang, H. T., Hung, V. Ph. & Nguyen, T. T. (2019). Immobilization of Protein A on Monodisperse Magnetic Nanoparticles for Biomedical Applications. Journal of Nanomaterials, 2182471. https://doi.org/10.1155/2019/2182471 [in English].
Wani, W. A., Prashar, S., Shreaz, Sh. & Gómez–Ruiz, S. (2016). Nanostructured materials functionalized with metal complexes: in search of alternatives for administering anticancer metallodrugs. Coordination Chemistry Reviews, 312(1), 67–98. https://doi.org/10.1016/
j.ccr.2016.01.001 [in English].
Wu, Y., Wang, Y., Luo, G. & Dai, Y. (2009). In situ preparation of magnetic Fe3O4–chitosan nanoparticles for lipase immobilization by cross–linking and oxidation in aqueous solution. Bioresource Technology, 100(14), 3459–3464. https://doi.org/10.1016/j.biortech.2009.02.018 [in English].
Wu, W., Wu, Z., Yu, T., Jiang, C. & Kim, W. S. (2015). Recent progress on magnetic iron oxide nanoparticles: synthesis, surface functional strategies and biomedical applications. Science and Technology of Advanced Materials, 16(2), 023501. https://doi.org/10.1088/1468-6996/16/2/023501 [in English].
Zhu, A., Lanhua, Y., Wenjie, J., Sheng, D. & Qianqian, W. (8009). Polysaccharide surface modified Fe3O4 nanoparticles for camptothecin loading and release. Acta Biomaterialia, 5(5), 1489–1498. https://doi.org/10.1016/j.actbio.2008.10.022 [in English].
Zhu, X., Gu, J., Li, Y., Zhao, W. & Shi, J. (2014). Magnetic сore–mesoporous shell nanocarriers with drug anchorages suspended in mesopore interior for cisplatin delivery. Microporous and Mesoporous Materials, 196(15), 115–121. https://doi.org/10.1016/j.micromeso.2014.04.057 [in English].
Gorbyk, P. P., Turelyk, M. P., Gorobets, S. V., Gorobets, O. Yu. & Demianenko, I. V. (2013). Biofunktsionalizovani nanomaterialy i nanokompozyty: naukovi osnovy ta napriamy zastosuvannia: navchalnyi posibnyk [Biofunctionalized nanomaterials and nanocomposites: scientific foundations and directions of application: monograph]. Kyiv: NTUU «KPI», 480 p. [in Ukrainian].
Kusiak, N. V., Svyrydiuk, K. P., Kychkyruk, O. Yu., Lystvan, V. V. & Gorbyk, P. P. (2025a). Kyslotno-osnovni vlastyvosti poverkhni nanorozmirnoho Fe3O4 [Acid-base properties of the surface of nanoscale Fe3O4]. Ukrainskyi zhurnal pryrodnychykh nauk [Ukrainian Journal of Natural Sciences], 12, 138–145. https://doi.org/10.32782/naturaljournal.12.2025.13 [in Ukrainian].
Kusiak, N. V., Svyrydiuk, K. P., Khodyuk, O. V., Kusyak, A. P. & Gorbyk, P. P. (2025b). Sorbtsiini kharakterystyky nanorozmirnoho Fe3O4 shchodo imunohlobulinu liudyny Ig [Sorption characteristics of nanoscale Fe3O4 regarding human immunoglobulin Ig]. Ukrainskyi zhurnal pryrodnychykh nauk [Ukrainian Journal of Natural Sciences], 14, 140–149. https://doi.org/10.32782/naturaljournal.14.2025.13 [in Ukrainian].
Semko, L. S., Hutornyy, S. V., Storozhuk, L. P., Dzyubenko, L. S., Abramov, N. V. & Gorbyk, P. P. (2010). Khimichne konstruiuvannia ta doslidzhennia vlastyvostei mahnыtokerovanykh adsorbentiv dlia ekstraktsii nukleinovykh kyslot [Chemical engineering and research the properties of magnetically operated adsorbents for the extraction of nucleic acids]. Poverkhnia [Surface], 2(17), 330–339. https://surfacezbir.com.ua/index.php/surface/article/view/423/421 [in Ukrainian].
