Volume 5 Number 1 2026
Nanoparticle-Mediated Ferroptosis Induction Combined with MRI Monitoring in Therapy-Resistant Cancers
Long Chiau Ming 1* Ong Khang Wei 2, Nurul Dayana Binti Mahizir 2
Biosensors and Nanotheranostics 5 (1) 1-8 https://doi.org/10.25163/biosensors.5110997
Submitted: 06 September 2026 Revised: 01 November 2026 Accepted: 07 November 2026 Published: 09 November 2026
Therapy-resistant solid tumours remain among the most intractable problems in clinical oncology, in large part because the mainstays of treatment converge on a single death programme—apoptosis—that resistant cells and cancer stem cells learn to evade. Ferroptosis, an iron-dependent form of regulated cell death driven by unchecked lipid peroxidation, sidesteps these classical escape routes and has therefore drawn intense interest. Yet the small-molecule inducers that first revealed its promise are limited by poor solubility, rapid clearance, and off-target toxicity. This review examines how rationally engineered nanomaterials—superparamagnetic iron oxide nanoparticles, metal–organic frameworks, catalytic nanozymes, and biomimetic membrane-camouflaged carriers—address these liabilities while simultaneously acting as magnetic resonance imaging (MRI) contrast agents, uniting therapy and diagnosis within one platform. We trace the molecular logic of ferroptosis through the System X??–glutathione–GPX4 axis, the labile iron pool, and Fenton chemistry, and describe how nanoplatforms exploit tumour iron addiction to deplete antioxidant defences, reverse multidrug efflux, and eradicate stem-like populations. We then consider the biophysics of T1, T2, and switchable dual-mode contrast that permits real-time tracking of biodistribution, accumulation, and early therapeutic response. Across preclinical models, nanoferroptosis combined with photothermal, sonodynamic, and radiotherapeutic actuation yields supra-additive responses and, through damage-associated molecular pattern release and cGAS–STING activation, converts immunologically cold tumours into inflamed niches responsive to checkpoint blockade. Finally, we weigh the translational obstacles—protein corona formation, long-term iron clearance, manufacturing reproducibility, and predictive modelling—that still separate compelling benchtop data from clinical reality. On balance, the evidence invites cautious optimism rather than certainty, since dependable clinical translation is not yet assured.
Keywords: ferroptosis; iron oxide nanoparticles; MRI theranostics; multidrug resistance; cancer stem cells; cGAS–STING; tumour microenvironment; immunogenic cell death.
Anani, T., Rahmati, S., Sultana, N., & David, A. E. (2021). MRI-traceable theranostic nanoparticles for targeted cancer treatment. Theranostics, 11(2), 579-601. https://doi.org/10.7150/thno.48811
Bilbao-Asensio, M., Zabaleta, A., Sosnowska, D., Arnold, J. N., & Mareque-Rivas, J. C. (2022). Peroxidase-mimetic magnetic iron oxide nanoparticles loaded with platinum(IV) prodrugs trigger ferroptosis and chemodynamic therapy in cancer. Advanced Therapeutics, 5(10), Article 2200088.
Chai, H., Xia, R., Ouyang, N., Yao, J., Hu, J., Sun, M., & Miao, P. (2025). Membrane encapsulated Fe3O4@MnO@cGAMP nanocatalyst for cancer therapy: cGAS-STING immune pathway activation. Advanced Healthcare Materials, 14(15), Article e2501587. https://doi.org/10.1002/adhm.202501587
Chen, C., Du, W., Jing, W., Sun, P., Shi, C., & Zhang, Y. (2022). Leveraging tumor cell ferroptosis for colorectal cancer treatment via nanoelicitor-activated tumoricidal immunity. Chemical Engineering Journal, 430, Article 132983. https://doi.org/10.1016/j.cej.2021.132983
Chen, H., Wang, D., Liu, J., Chen, J., Hu, Y., & Ni, Y. (2025). Augmenting antitumor immune effects through the coactivation of cGAS-STING and NF-κB crosstalk in dendritic cells and macrophages by engineered manganese ferrite nanohybrids. ACS Applied Materials & Interfaces, 17(9), 13375-13390. https://doi.org/10.1021/acsami.4c18570
Chen, H., Yan, Z., Wu, S., & Li, F. (2021). A glutathione-responsive polyphenol-constructed nanodevice for double roles in apoptosis and ferroptosis. Colloids and Surfaces B: Biointerfaces, 205, Article 111902. https://doi.org/10.1016/j.colsurfb.2021.111902
Chen, Y., Li, X., Luo, K., Wang, T., Liu, T., Lu, E., & Shen, Q. (2024). Hyperthermia/glutathione-triggered ferritin nanoparticles amplify the ferroptosis for synergistic tumor therapy. Materials Today Bio, 26, Article 101085. https://doi.org/10.1016/j.mtbio.2024.101085
Chen, Y., Yao, Z., Liu, P., Hu, Q., Huang, Y., Ping, L., & Shen, Q. (2023). A self-assembly nano-prodrug for triple-negative breast cancer combined treatment by ferroptosis therapy and chemotherapy. Acta Biomaterialia, 159, 275-288. https://doi.org/10.1016/j.actbio.2023.01.050
Deng, X., Liu, T., Zhu, Y., Chen, J., Song, Z., Shi, Z., & Chen, H. (2024). Ca & Mn dual-ion hybrid nanostimulator boosting anti-tumor immunity via ferroptosis and innate immunity awakening. Bioactive Materials, 33, 483-496. https://doi.org/10.1016/j.bioactmat.2023.11.017
Ding, Q., Tang, W., Li, X., Ding, Y., Chen, X., Cao, W., Wang, X., Mo, W., Su, Z., Zhang, Q., & Shen, Q. (2023). Mitochondrial-targeted brequinar liposome boosted mitochondrial-related ferroptosis for promoting checkpoint blockade immunotherapy in bladder cancer. Journal of Controlled Release, 363, 221-234. https://doi.org/10.1016/j.jconrel.2023.09.024
Ensoy, M., Bumin, Z. S., Jama, H. A., & Cansaran-Duman, D. (2024). Inducing ferroptosis via nanomaterials: A novel and effective route in cancer therapy. Journal of Physics: Materials, 7(3), Article 032003. https://doi.org/10.1088/2515-7639/ad4d1e
Ge, H., Du, J., Zheng, J., Xu, N., Yao, Q., Long, S., & Xiao, Y. (2022). Viscosity-dependent photocatalysis triggers ferroptosis and type-I photodynamic therapy to kill drug-resistant tumors. Chemical Engineering Journal, 449, Article 136565. https://doi.org/10.1016/j.cej.2022.136565
Gupta, A., Niveria, K., Chandpa, H. H., Singh, M., Kumar, V., Panda, A. K., & Meena, S. (2024). Monitoring ROS responsive Fe3O4-based nanoparticle mediated ferroptosis and immunotherapy via ¹²?Xe MRI. Angewandte Chemie International Edition, 63(26), Article e202403771.
Han, S., Zou, J., Xiao, F., Xian, J., Liu, Z., Li, M., Luo, W., Feng, C., & Kong, N. (2024). Nanobiotechnology boosts ferroptosis: Opportunities and challenges. Journal of Nanobiotechnology, 22(1), Article 606. https://doi.org/10.1186/s12951-024-02842-5
He, H., Du, L., Xue, H., An, Y., Zeng, K., Huang, H., He, Y., Zhang, C., Wu, J., & Shuai, X. (2023). Triple tumor microenvironment-responsive ferroptosis pathways induced by manganese-based imageable nanoenzymes for enhanced breast cancer theranostics. Small Methods, 7(9), Article e2300230. https://doi.org/10.1002/smtd.202300230
Hou, D. Y., Cheng, D. B., Zhang, N. Y., Wang, Z. J., Hu, X. J., Li, X., & Liu, Z. (2024). In vivo assembly enhanced binding effect augments tumor specific ferroptosis therapy. Nature Communications, 15(1), Article 454. https://doi.org/10.1038/s41467-023-44665-2
Jiang, Q., Wang, K., Zhang, X., Ouyang, B., Liu, H., Pang, Z., & Yang, W. (2020). Platelet membrane-camouflaged magnetic nanoparticles for ferroptosis-enhanced cancer immunotherapy. Small, 16(22), Article 2001704. https://doi.org/10.1002/smll.202001704
Kesharwani, P., & Gao, F. (2024). Nanoparticle-mediated ferroptosis: Overcoming barriers in cancer therapy. Nano-Micro Letters, 16(1), Article 199. https://doi.org/10.1007/s40820-024-01399-0
Li, C., Zhao, W., Geng, D., Jin, Y., & Guan, W. (2025). Targeting the interplay of cGAS-STING and ferroptosis by nanomedicine in the treatment of cancer. Journal of Hematology & Oncology, 18(1), Article 45. https://doi.org/10.1186/s13046-025-03520-6
Li, L. G., Yang, X. X., Xu, H. Z., Yu, T. T., Li, Q. R., Hu, J., Peng, X. C., Han, N., Xu, X., Chen, N. N., & Wang, H. (2023). A dihydroartemisinin-loaded nanoreactor motivates anti-cancer immunotherapy by synergy-induced ferroptosis to activate cGAS/STING for reprogramming of macrophage. Advanced Healthcare Materials, 12(31), Article e2301561. https://doi.org/10.1002/adhm.202301561
Li, Z., Wu, X., Wang, W., Gai, C., Zhang, W., Li, W., & Ding, D. (2021). Fe(II) and tannic acid-cloaked MOF as carrier of artemisinin for supply of ferrous ions to enhance treatment of triple-negative breast cancer. Nanoscale Research Letters, 16(1), Article 37. https://doi.org/10.1186/s11671-021-03497-z
Liang, J. L., Jin, X. K., Zhang, S. M., Huang, Q. X., Ji, P., Deng, X. C., Cheng, S. X., Chen, W. H., & Zhang, X. Z. (2023). Specific activation of cGAS-STING pathway by nanotherapeutics-mediated ferroptosis evoked endogenous signaling for boosting systemic tumor immunotherapy. Science Bulletin, 68(6), 622-636. https://doi.org/10.1016/j.scib.2023.02.027
Liang, S., Yao, J., Liu, D., Rao, L., Chen, X., & Wang, Z. (2021). Harnessing nanomaterials for cancer sonodynamic immunotherapy. Advanced Materials, 33(35), Article e2101224. https://doi.org/10.1002/adma.202211130
Nejadnik, H., Pandit, P., Loening, A., Gambhir, S. S., & Daldrup-Link, H. E. (2017). Ferumoxytol-derived dual-modality imaging probe for monitoring stem cell therapies and tumor margins. Nature Biomedical Engineering, 1(8), Article 0092.
Peng, H., Zhang, X., Yang, P., Zhao, J., Zhang, W., Feng, N., & Shen, Q. (2023). Defect self-assembly of metal-organic framework triggers ferroptosis to overcome resistance. Bioactive Materials, 19, 1-11. https://doi.org/10.1016/j.bioactmat.2021.12.018
Qin, Y., Liu, X., Zhang, M., Chen, T., & Wang, L. (2025). Dual-responsive CuMnO\@Fe3O4 core-shell nanozyme for MRI-guided tumor theranostics and synergistic ferroptosis-photothermal ablation. Chemical Communications, 61(12), 1740-1755.
Roshanghias, H., Ganjavinia, N., Zarei-Shokat, S., & Maleki, A. (2026). An overview on the multifunctional nanozyme activities of iron oxide magnetic nanoparticles for nanomedicine. Materials Advances, 7(13), 6971-6992. https://doi.org/10.1039/D5MA01508A
Sang, M., Luo, R., Bai, Y., Dou, J., Zhang, Z., Liu, F., Feng, F., Xu, J., & Liu, W. (2019). Mitochondrial membrane anchored photosensitive nano-device for lipid hydroperoxides burst and inducing ferroptosis to surmount therapy-resistant cancer. Theranostics, 9(21), 6209-6223. https://doi.org/10.7150/thno.36283
Song, X., Xiao, L., Xu, L., Jiang, Y., Fu, W., Chen, B., Zheng, W., Qian, H., & Yu, Y. (2025). Fe3O4@Bi2S3 nanoparticles mediated MRI-guided precision radiosensitization for orthotopic glioblastoma via external magnetism. ACS Applied Materials & Interfaces, 17(14), 21478-21490. https://doi.org/10.1021/acsami.5c01498
Suh, M., Park, J. Y., Ko, G. B., Kim, J. Y., Hwang, D. W., Rees, L., Conway, G. E., Doak, S. H., Kang, H., & Lee, N. (2024). Optimization of micelle-encapsulated extremely small sized iron oxide nanoparticles as a T1 contrast imaging agent: Biodistribution and safety profile. Journal of Nanobiotechnology, 22(1), Article 419. https://doi.org/10.1186/s12951-024-02699-8
Wang, H., Guan, Y., Li, C., Chen, J., Yue, S., Qian, J., Dai, B., Jiang, C., Wen, C., & Wen, L. (2023). PEGylated manganese-zinc ferrite nanocrystals combined with intratumoral implantation of micromagnets enabled synergetic prostate cancer therapy via ferroptotic and immunogenic cell death. Small, 19(38), Article 2207077. https://doi.org/10.1002/smll.202207077
Wang, L., Huang, J., Chen, H., Wu, H., Xu, Y., Li, Y., Yi, H., Wang, Y. A., Yang, L., & Mao, H. (2017). Exerting enhanced permeability and retention effect driven delivery by ultrafine iron oxide nanoparticles with T1-T2 switchable magnetic resonance imaging contrast. ACS Nano, 11(5), 4582-4592. https://doi.org/10.1021/acsnano.7b00038
Wang, X., Luo, J., Zeng, X., & Yan, S. (2025). Ferroptosis by nanomaterials: targeting cancer stem cells and overcoming drug resistance. Acta Materia Medica, 4(3), 358-389.
Wang, X., Zhao, L., Wang, C., Wang, L., Wu, H., Song, X., & Shen, Q. (2023). Potent nanoreactor-mediated ferroptosis-based strategy for the reversal of cancer chemoresistance to sorafenib. Acta Biomaterialia, 159, 237-246. https://doi.org/10.1016/j.actbio.2023.01.053
Wang, Z., Xiao, P., Guo, Y., Zheng, Z., Wang, X., & Yang, C. (2025). Inducing ferroptosis in breast cancer with nanoparticles: A promising and challenging therapeutic strategy. Journal of Materials Chemistry B, 13(42), 13567-13588. https://doi.org/10.1039/D5TB00768B
Wu, K., Zhang, W., Chen, H., Wu, J., Wang, X., Yang, X., & Liu, Z. (2023). An iron oxyhydroxide-based nanosystem sensitizes ferroptosis by a "three-pronged" strategy in breast cancer stem cells. Acta Biomaterialia, 160, 281-296. https://doi.org/10.1016/j.actbio.2023.02.015
Xie, M., Li, Y., Xu, Y., Wang, L., Huang, J., & Mao, H. (2022). Brain tumor imaging and delivery of sub-5 nm magnetic iron oxide nanoparticles in an orthotopic murine model of glioblastoma. ACS Applied Nano Materials, 5(7), 9706-9718. https://doi.org/10.1021/acsanm.2c01930
Xie, Q., Wang, X., Zhang, G., Zhou, D., Zhao, Y., Liu, H., Duan, J., Yu, D., & Sang, Y. (2024). Ultrasmall Fe3O4 nanoparticles self-assembly induced dual-mode T1/T2-weighted magnetic resonance imaging and enhanced tumor synergetic theranostics. Scientific Reports, 14(1), Article 10646. https://doi.org/10.1038/s41598-024-59525-2
Xu, Q., Zhan, G., Zhang, Z., Yong, T., Yang, X., & Gan, L. (2021). Manganese porphyrin-based metal-organic framework for synergistic sonodynamic therapy and ferroptosis in hypoxic tumors. Theranostics, 11(4), 1937-1952. https://doi.org/10.7150/thno.45511
Yang, C., Li, S., & Wang, L. (2025). Engineered iron oxide nanoplatforms: Reprogramming immunosuppressive niches for precision cancer theranostics. Molecular Cancer, 24(1), Article 225. https://doi.org/10.1186/s12943-025-02443-2
Yang, R., Li, Y., Wang, X., Yan, J., Pan, D., Xu, Y., Wang, L., & Yang, M. (2021). Doxorubicin loaded ferritin nanoparticles for ferroptosis enhanced targeted killing of cancer cells. RSC Advances, 9(49), 28548-28553. https://doi.org/10.1039/C9RA04478G
Zeng, X., & Yan, S. (2025). Targeting tumor ferroptosis with nanomaterials: Eradicating cancer stem cells and overcoming drug resistance. Antioxidants & Redox Medicine, 2(2), Article AMM20240083.
Zhang, F. (2026). Magnetic nanoparticles as a theranostic platform for brain tumors: Mechanistic framework, translational barriers, and clinical perspectives. International Journal of Nanomedicine, 21, 1-28. https://doi.org/10.2147/IJN.S611920
Zhao, H., Jin, S., Liu, Y., Wang, Q., Tan, B., Wang, S., Han, W. K., Niu, X., & Zhao, Y. (2025). A second near-infrared window-responsive metal-organic-framework-based photosensitizer for tumor immunotherapy via synergistic ferroptosis and STING activation. Journal of the American Chemical Society, 147(6), 4871-4885. https://doi.org/10.1021/jacs.4c13241
Zhao, Z., Wu, Y., Liang, X., Liu, J., Luo, Y., Zhang, Y., & Shen, Q. (2023). Sonodynamic therapy of NRP2 monoclonal antibody-guided MOFs@COF targeted disruption of mitochondrial and endoplasmic reticulum homeostasis to induce autophagy-dependent ferroptosis. Advanced Science, 10(31), Article e2303872. https://doi.org/10.1002/advs.202303872
Zhou, L., Dong, C., Ding, L., Feng, W., Yu, L., Cui, X., & Chen, Y. (2021). Targeting ferroptosis synergistically sensitizes apoptotic sonodynamic anti-tumor nanotherapy. Nano Today, 39, 101212.
Bovine Mastitis in Bangladesh: Prevalence, Bacterial Aetiology, and Antimicrobial Resistance-A One Health Perspective