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Smart and Multi-Functional Magnetic Nanoparticles for Cancer Treatment Applications: Clinical Challenges and Future Prospects
Abstract
Iron oxide nanoparticle (IONPs) have become a subject of interest in various biomedical fields due to their magnetism and biocompatibility. They can be utilized as heat mediators in magnetic hyperthermia (MHT) or as contrast media in magnetic resonance imaging (MRI), and ultrasound (US). In addition, their high drug-loading capacity enabled them to be therapeutic agent transporters for malignancy treatment. Hence, smartening them allows for an intelligent controlled drug release (CDR) and targeted drug delivery (TDD). Smart magnetic nanoparticles (SMNPs) can overcome the impediments faced by classical chemo-treatment strategies, since they can be navigated and release drug via external or internal stimuli. Recently, they have been synchronized with other modalities, e.g., MRI, MHT, US, and for dual/multimodal theranostic applications in a single platform. Herein, we provide an overview of the attributes of MNPs for cancer theranostic application, fabrication procedures, surface coatings, targeting approaches, and recent advancement of SMNPs. Even though MNPs feature numerous privileges over chemotherapy agents, obstacles remain in clinical usage. This review in particular covers the clinical predicaments faced by SMNPs and future research scopes in the field of SMNPs for cancer theranostics.
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![Figure 2 Preparation of di-block copolymer based on PEG and PCL. Reprinted with permission from [201]. Elsevier, 2018.](/paper-figures/fd52b30586bc4e88ba0a100de4132310/smart-and-multi-functional-magnetic-nanoparticles-for-cancer-treatment-figure-2.jpg)
![Figure 3 Enzyme-responsive, glycine-coated, MTX-conjugated Fe3O4 NPs. Redrawn from [209].](/paper-figures/cf7b9a43169a4727a48ce17a690a8d27/smart-and-multi-functional-magnetic-nanoparticles-for-cancer-treatment-figure-3.jpg)
![Figure 4 Schematic representation of a triple stimuli-responsive MNP drug carrier. Redrawn from [261].](/paper-figures/5be89f70c20d4ea6944c4db02e19e092/smart-and-multi-functional-magnetic-nanoparticles-for-cancer-treatment-figure-4.jpg)
![Figure 5 Schematic representation of an in vivo experimental procedure and the active targeting of DOX, and the cellular uptake by 4T1 cells following the administration. Redrawn from [282].](/paper-figures/ccfe5fb9348540c1a079ff6adde66b9d/smart-and-multi-functional-magnetic-nanoparticles-for-cancer-treatment-figure-5.jpg)
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“These limitations span across synthesis, scalability, reproducibility, regulatory compliance, and long-term safety [93].”
From Advances in green-synthesized magnetic nanoparticles for targeted cancer therapy: mechanisms, applications, and future perspectives (2026) · cites this paper as [93]
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“Despite the considerable potential of magnetic nanoparticles (MNPs) in cancer therapy, several challenges and limitations must be addressed before they can be widely adopted in clinical practice.”
From Advances in green-synthesized magnetic nanoparticles for targeted cancer therapy: mechanisms, applications, and future perspectives (2026) · cites this paper as [93]
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Cellular uptake of nanoparticles: Journey inside the cell
Behzadi, S., Serpooshan, V., Tao, W., Hamaly, M. A., Alkawareek, M. Y., Dreaden, E. C., Brown, D., Alkilany, A. M., Farokhzad, O. C., & Mahmoudi, M. (2017) · Chemical Society Reviews · doi:10.1039/c6cs00636a · Cited by 2,859
Progress and challenges towards targeted delivery of cancer therapeutics
Rosenblum, D., Joshi, N., Tao, W., Karp, J. M., & Peer, D. (2018) · Nature Communications · doi:10.1038/s41467-018-03705-y · Cited by 2,220
In vivo delivery, pharmacokinetics, biodistribution and toxicity of iron oxide nanoparticles
Arami, H., Khandhar, A., Liggitt, D., & Krishnan, K. M. (2015) · Chemical Society Reviews · doi:10.1039/c5cs00541h · Cited by 830
A Review of Clinical Translation of Inorganic Nanoparticles
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Review of Stimuli-Responsive Polymers in Drug Delivery and Textile Application
CHATTERJEE, S., & Chi-leung HUI, P. (2019) · Molecules · doi:10.3390/molecules24142547 · Cited by 201
Iron oxide-loaded nanotheranostics: major obstacles to in vivo studies and clinical translation
Schleich, N., Danhier, F., & Préat, V. (2015) · Journal of Controlled Release · doi:10.1016/j.jconrel.2014.11.024 · Cited by 124
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El-khawaga, A. M., Youssef, O. I., El-dydamoni, O. A., Ragab, W. M., & Mohammed, R. A. E. (2026) · European Journal of Medical Research · doi:10.1186/s40001-025-03804-9 · Cited by 14
Metadata
- Authors
- Aram, E., Moeni, M., Abedizadeh, R., Sabour, D., Sadeghi-Abandansari, H., Gardy, J., & Hassanpour, A.
- Venue
- Nanomaterials
- Publisher
- MDPI AG
- Published
- 2022-10-12
- Volume
- 12
- Issue
- 20
- Pages
- 3567
- ISSN
- 2079-4991
- PMC
- PMC9611246
- Cited by
- 66
- References
- 6
- Language
- en
- Funders
- Royan institute for Stem Cell Biology and Technology
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