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Review

Use of Iron in Modulation of Ferroptosis as Therapeutic Strategy in Breast Cancer: A Scoping Review

by
Érika Leite Ferraz Libório
1,
Karine de Cássia Freitas
1,
Arnildo Pott
2,
Rosângela dos Santos Ferreira
1,
Aline Carla Inada
1,
Priscila Aiko Hiane
1,
Juliana Rodrigues Donadon
3,
Valter Aragão do Nascimento
1 and
Rita de Cássia Avellaneda Guimarães
1,*
1
Graduate Program in Health and Development in the Central-West Region of Brazil, Federal University of Mato Grosso do Sul, Campo Grande 79070-900, MS, Brazil
2
Laboratory of Botany, Institute of Biosciences, Federal University of Mato Grosso do Sul, Campo Grande 79070-900, MS, Brazil
3
Pharmaceutical Science, Food and Nutrition Faculty, Federal University of Mato Grosso do Sul, Campo Grande 79070-900, MS, Brazil
*
Author to whom correspondence should be addressed.
Sci 2026, 8(6), 130; https://doi.org/10.3390/sci8060130
Submission received: 12 February 2026 / Revised: 18 April 2026 / Accepted: 26 May 2026 / Published: 2 June 2026
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Abstract

The tumor microenvironment of breast cancer presents high complexity and resistance to conventional therapies. Ferroptosis, a programed cell death that is dependent on iron and characterized by lipid peroxidation, arises as a promising therapeutic goal. This scoping review mapped evidence on the exogenous use of iron and selenium, in conventional or nano-particulated forms, in the modulation of ferroptosis as therapeutic strategy for breast cancer treatment, identifying knowledge gaps and opportunities for future research. We performed a scoping review and the methodology followed the guidelines of the Joanna Briggs Institute (JBI) and PRISMA-ScR. We made a systematic search in five data bases (Embase, Lilacs, PubMed (MEDLINE), Scopus, and Web of Science) between the years 2012 and 2025. Among 2.723 identified publications, we selected 48 studies. The results revealed predominance of nanoplatforms of iron (97.9%), focused on the Fenton reaction. The modulation of selenium for inactivation of GPX4 was shown to be effective, though still little-explored (n = 1). We evidenced that the induction of ferroptosis potentializes tumor immunogenicity and the effectiveness of combined therapies. We conclude that the field is under development; thus, the diversification of metabolic targets and trials of chronic toxicity are fundamental steps for future clinical research.

1. Introduction

Breast cancer still is a global challenge in public health, characterized by a molecular heterogeneity that leads to chemotherapeutic resistance, mainly in the triple negative (TNBC) subtype. In the face of the limitations of conventional therapies, the search for non-apoptotic cell death mechanisms has become strategic. In this scenario, ferroptosis, a category of programed cell death dependent on iron and defined by lethal lipid perox-idation, arises as a promising metabolic alternative for the treatment of tumor cells [1,2].
Ferroptosis is controlled by the balance between the production of oxidative damages and cell defense, and it occurs when there is a lethal buildup of reactive species of oxygen (ROS), which deregulate the repairing system of lipid peroxides. Iron, in this reaction, acts as the leading generator of free radicals through the Fenton reaction (Fe2+ + H2O2 → Fe3+ + ●OH + OH−), catalyzing the conversion of hydrogen peroxides into highly reactive hydroxyl radicals (●OH). As a counterpart, selenium is essential for the functionality of the enzyme glutathione peroxidase 4 (GPX4), which protects the cell from such damage [3].
GPX4 is a selenoprotein that requires selenium for its synthesis and catalytic activity in the active site, being the only enzyme capable of reducing complex lipid peroxides into non-toxic lipid alcohols in the double layer of phospholipids, and hence serving as a metabolic protector against ferroptosis. Therefore, its depletion or pharmacological inhibition makes cancer cells vulnerable to oxidative cell death. Thus, the use of iron to increase oxidative stress or the manipulation of selenium to inhibit cell protection are viable paths for the treatment of breast tumors [4,5].
In this context, nanotechnology arises as a relevant tool. The development of nano-platforms containing iron and selenium allows for these nutrients to be delivered directly to the tumor, which increases the effectiveness of the treatment and reduces the systemic toxicity [6]. However, since evidence of those interactions is dispersed in the literature, this scoping review was established to synthesize the role of these elements in the induction of cell death and offer new therapeutic perspectives on this theme.
The objective of this scoping review was to map and synthesize how the use of iron and selenium, in conventional or nanoparticulated forms, modulates ferroptosis in breast cancer, identifying the present state of knowledge and the gaps that need to be studied for these strategies to reach clinical practice.

2. Materials and Methods

This scoping review was conducted in accordance with the international guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) [7]. The complete PRISMA-ScR checklist is provided in the Supplementary Materials (Checklist S1). The methodology followed the framework proposed by the Joanna Briggs Institute (JBI) [8], with the objective of mapping the use of exogenous iron and selenium, in conventional or nanoparticulated forms, as a strategy to modulate ferroptosis in breast cancer treatment. The protocol for this review was prospectively registered on the Open Science Framework (OSF) [9].
The research question was developed using the PCC framework: population (in vitro breast cancer cell lines, in vivo animal models, and humans with breast cancer); concept (exogenous iron and/or selenium, including nanostructures, focused on ferroptosis mod-ulation); and context (oncological treatment and ferroptosis as a therapeutic target).
The searches were carried out in October 2025 across the PubMed/MEDLINE, Scopus, Web of Science, Embase, and LILACS databases (Figure 1). The full electronic search strategy used for the PubMed/MEDLINE database is provided in the Supplementary Materials (Table S1). Validated descriptors from MeSH, DeCS, and Emtree were used in English, Portuguese, and Spanish, including: Breast Neoplasms; Triple Negative Breast Neo-plasms; Iron; Selenium; Ferroptosis; Nanoparticles.
Original studies published between 2012 and 2025 were included, marking the period since the formalization of the concept of ferroptosis. Eligible documents included primary research (in vitro, in vivo, and clinical trials) written in Portuguese, English, or Spanish. Exclusion criteria comprised studies that did not involve the exogenous administration of iron or selenium, research focused exclusively on endogenous metabolism without therapeutic intervention, reviews, editorials, and abstracts without full-text availability.
Study selection was performed independently by two reviewers in two stages: (i) title and abstract screening, and (ii) full-text assessment of eligible records. The process was managed using the Rayyan software, version 1.4.3, with disagreements resolved by consensus. Data extracted included: bibliographic information, experimental models, type of nutrient/nanoparticle, molecular mechanisms of ferroptosis induction, and main therapeutic outcomes. The synthesis was descriptive and is presented in both narrative and tabular formats.

3. Results

The findings were organized in four main axes: selected studies and bibliometric distribution; experimental models; nanotechnological platforms; and mechanisms of molecular action. This structure allowed for a comprehensive understanding of technological advances, of the predominance of the Fenton reaction mediated by iron release, and of present gaps in therapies focused on selenium.

3.1. Study Selection and Bibliometric Analysis

The identification and selection of studies, detailed in the PRISMA-ScR flowchart (Figure 1), led to 2723 publications being found. After removing duplicates and sorting, 515 articles advanced to the full review, resulting in the exclusion of 467 for not fulfilling the eligibility criteria. Thus, a total of 48 original studies were included (Table 1). The physical–chemical properties of the nanosystems, such as particle size, were cataloged to evaluate their potential for tumor accumulation via the enhanced permeability and retention (EPR) effect.
The analysis of particle size (Table 1) revealed that most nanoformulations (81.2%) were projected in the range of 50–200 nm. According to the literature, that distribution of size is considered ideal to avoid fast renal depuration, which is associated with particles smaller than 10 nm and maximizes the intratumoral buildup through the effects of Enhanced Permeability and Retention (EPR) [58].
This size range balances the need for prolonged systemic circulation to avoid the splenic and hepatic filtration that frequently remove particles above 200 nm [58]. Such parameters are critical for the clinic translation of iron-based therapies for breast cancer, since they assure efficient penetration into the tumor parenchyma and higher therapeutic suppression [59]. In addition, the maintenance of sizes within this ideal window favors the development of theranostic platforms, integrating the magnetic properties of iron for imaging within the directed induction of ferroptosis [60].
The bibliometric analysis revealed a significant concentration of research originating from China, responsible for 89.5% (n = 43) of the sample. This trend reflects substantial institutional investment and the expansion of the Chinese strategic roadmap in nanobiomedicine and ferroptosis research over the last five years. From this total, 40 studies were carried out by China alone, and the other 3 were international collaborations with Italy, South Korea, and Singapore, evidencing the relevance of China in the development of nanosystems applied to ferroptosis. It was also possible to observe that countries such as Italy, Germany, Austria, Egypt, Spain, India, and Taiwan still have few studies in this area (Figure 2).
Regarding the temporal distribution of the included studies (Figure 3), we observed a growing interest in the theme in studies published between the years 2020 and 2025, with a peak of publications concentrated in 2024 (n = 19), representing 39.6%.
The periodicals that published the most studies related to these themes were the Journal of Nanobiotechnology, and Biomaterials, which led the publications (n = 5 each), followed by ACS Nano (n = 3), providing the main references in this area.

3.2. Methodologic Design and Experimental Models

Table 2 shows the experimental models utilized in the included studies, covering the type of design, the applied cell lineages, the animal models, and the investigated breast cancer subtypes. The systematization of these data allows for a broad view of the biological models adopted to evaluate the induction of ferroptosis.
The predominant methodological approach was the combined use of in vitro and in vivo models, identified in 91.6% of studies (n = 44). Three studies were conducted exclusively in vitro, while only one validated its findings by integrating in vitro, in vivo and human clinical breast cancer samples, representing the highest level of evidence among the included studies (Figure 4).
In the in vivo experimental context, we verified the predominance of the syngeneic murine model (n = 40), which exclusively utilized the 4T1 murine lineage in BALB/c mice. This methodological choice is strategic, as it allows for the evaluation of ferroptosis within a tumor microenvironment with an intact immune system, mirroring the aggressive and metastatic behavior of human TNBC [61].
Xenograft models were applied in 15 studies employing human lineages, such as MDA-MB-231 and MCF-7, in immunosuppressed mice. We point out that the 4T1 lineage was the most frequently utilized overall (n = 40), consolidating itself as the gold standard for studies focusing on aggressiveness and metastasis in ferroptosis induction.
Malignant cell lines (Figure 5) were categorized according to their biological origin and molecular profile, as detailed in Table 2. These models include both murine (Figure 5a) and human (Figure 5b) origins, providing a comprehensive perspective on ferroptosis sensitivity across different species and subtypes.
Some studies utilized non-malign cell linens and coculture trials to assure the ferroptosis induction in TME and reduce the cytotoxic effects on healthy stroma. Hence, research focused on specialized subpopulations and overcoming resistance, utilizing strategies such as gene silencing or enzymatic inhibition, should be studied as promising approaches to face the molecular heterogeneity of advanced breast cancer.

3.3. Inductor Agents and Nanotechnological Platforms

The identified interventions are dominated by advanced nanotechnologies. Nearly all studies were concentrated on the induction of ferroptosis by iron overload (n = 47; 97.9%) to catalyze Fenton’s reaction to produce ●OH. In contrast, we identified few studies exploring selenium (n = 1; 2.1%), which utilized sodium selenite (Na2SeO3) as a direct modulator of the enzymatic path GPX4, evidencing a relevant research gap on non-ferrous cofactors in the present literature.
The delivery platforms are classified into six functional categories (Table 3).
The MOFs, and the nanozymes represented 29.2%, followed by iron oxides and SPIONs (20.8%). MOFs presented higher versatility, being applied as catalytic nanoreactors and drug delivery vehicles for combined therapies. The group of PDA and MPNs (n = 8, 16.7%) demonstrated a trend toward multimodal therapy, benefiting from the photothermic properties of the iron–polyphenol complexes and polydopamine to potentize ferroptosis via PTT.
Concerning therapeutic strategies, multimodal therapy represented 39.6% of studies, characterized by the association of ferroptosis with external stimuli, such as photothermic (PTT) and sonodynamic therapies (SDT), to increase catalyzation through the Fenton reaction. Combined chemotherapy (37.5%) focused on sensitization to drugs such as doxorubicin, cisplatin, and camptothecin. In this context, the nanoparticles act as co-delivery platforms, utilizing ferroptosis to revert chemoresistance via inhibition of parallel axes such as DHODH and FSP1.
Immunotherapy was identified in 18.7% of studies, in which ferroptosis acted as a trigger for immunogenic cell death (ICD). This mechanism promotes the release of molecular patterns associated with damage (DAMPs), promoting the remodeling of the tumor microenvironment and activation of the immune antitumor response. Finally, adjuvant gene therapy (4,2%) was achieved through the use of siRNA (TRIM37, ACSL4) and hydrogels for the prevention of surgical recurrence.

3.4. Mechanisms of Action and Molecular Targets

The central induction mechanism was the Fenton reaction, present in 97.9% of works, resulting in oxidation in the membrane lipid chain through the intracellular release of iron ions (Fe2+/Fe3+), which react with endogenous or exogenous hydrogen peroxide (H2O2) (provided by bimetallic peroxides) to generate hydroxyl radicals (•OH), acting as a precursor of the ferroptosis process. In 39.6% (n = 19) of cases that utilized multimodal therapies (PTT or SDT), we verified that the production of these radicals was accelerated by external physical stimuli, increasing cell death kinetics compared with the isolated use of chemical agents.
The inhibition of the axis GPX4/SLC7A11 (System xc-) was the most-explored strategy (n = 36; 75%). To reach that objective, researchers utilized several approaches: 25% (n = 12) referrred to gene silencing via small interference RNAs (siRNA) or the delivery of microRNA (miRNA) to block the production of defense proteins (such as TRIM37, GPX4 and SLC7A11), while most focused on the direct exhaustion of glutathione (GSH) by means of the consumption of materials with intrinsic redox.
Regarding more recent studies, 16.6% identified alternative means of resistance, such as the DHODH, the FSP1 system and thioredoxin reductase (TrxR), which act as reserve defenses when the GPX4 path is blocked. In addition, ferroptosis was reported as an effective mechanism for the reversal of multidrug resistance (MDR) in 37.5% of cases, demonstrating that alterations in the membrane permeability by lipid peroxidation potentiate the effectiveness of adjacent chemotherapeutic drugs.

4. Discussion

4.1. Analysis of Temporal and Geographic Distribution

The modulation of ferroptosis by iron and selenium in breast cancer is an emergent field that has undergone rapid expansion in the last decade. Although the term “ferroptosis” was first described in 2012, the data in this review indicate that the application of specific nanosystems based on iron and selenium to enhance the treatment of breast cancer is a recent phenomenon. The productive peak in 2024 (39.6%) reflects the maturation of nanomedicine applied to tumor pathogenesis [62].
Regarding the geography of this research, China exerts absolute hegemony (89.5%), a result of strategic investments in centers of excellence such as the National Center for Nanoscience and Technology and the Center for Excellence in Nanoscience (CAS-CENano) [63]. This concentration suggests that the current global roadmap for ferroptosis research is heavily influenced by Chinese biomedical priorities. However, such centralization may limit the diversity of experimental models. The integration observed in collaborations such as Italy, South Korea, and Singapore suggests a necessary movement toward more comprehensive therapies, in which geographic diversity can enrich the understanding of the biological mechanisms in different genetic and clinical backgrounds.

4.2. Methodological Design

The predominance of integrated in vitro and in vivo approaches (91.6%) demonstrates consistent methodological rigor with oncological nanomedicine. Validation in animal models is indispensable to reproduce the complexity of the tumor microenvironment (TME), including the vascular dynamics and the extracellular matrix barriers, which cannot can be totally replicated in vitro [64,65].
The recurrent use of the 4T1 murine lineage in BALB/c mice stands out as a strategic choice. Since these are syngeneic models, they preserve the host’s immunocompetence, which is important for investigating ferroptosis not merely as a localized chemical event, but as a driver of Immunogenic Cell Death (ICD). This allows for the evaluation of how ferroptotic debris promotes the maturation of dendritic cells and the subsequent activation of T-lymphocytes within the TME.
However, xenograft models utilizing human cell lines such as MDA-MB-231 (n = 18) and MCF-7 (n = 13) in immunosuppressed mice remain essential. Those models provide a direct evaluation of the effectiveness of the nanotechnologies concerning specific human molecular profiles, mainly, mesenchymal, which is highly susceptible to the peroxidation of TNBC, as well as metabolic particularities of the subtype Luminal A [65]. Nevertheless, the shortage of validation in human samples (n = 1) indicates that the field is still in the initial pre-clinical phase, with trials of chronic toxicity and long-term administration still being required. To overcome that translational gap, future research should prioritize ex vivo trials with human primary cells and comprehensive profiles of toxicity in the long term, assuring the safety of chronic iron administration [66,67].

4.3. Nanosystems and Inductor Agents

Iron appeared as the central catalyst of ferroptosis in 97.9% of the analyzed literature, acting via Fenton reaction to generate highly toxic ●OH. It was reported that the architecture of the nanocarriers is directly related to the effectiveness of this catalytic process [67]. Thus, the diversity of Fe-containing nanosystems demonstrates that this component is consolidated as the leading element for the design of therapeutic strategies against aggressive subtypes, such as TNBC [68].
MOFs and manozymes (29.2%) stand out as catalytic nanoreactors with high porosity, which is fundamental for combined chemotherapy (37.5% of studies). Structures such as ZIF-8 and MIL-100 (Fe) allow for the co-delivery of drugs and siRNA, permitting the release of iron to occur in synergy with GSH depletion and the inactivation of GPX4 or DHODH, surpassing the cells’ oxidative resistance [69].
The use of SPIONs was identified in 20.8% of the works. These platforms offer a relevant theranostic functionality in addition to providing the Fe2+ necessary for ferroptosis. Due to their superparamagnetic properties, they allow for the application of magnetic hyperthermia via alternating magnetic fields, promoting localized heating that accelerates the intratumoral release of iron and intensifies ROS production [67,70,71,72].
Systems based on MPNs and PDA nanoparticles demonstrated a strong tendency toward multimodal therapy (39.6%). In these systems, near-infrared (NIR) laser stimuli potentiate ferroptosis by inactivating cellular antioxidant systems, serving as both a thermal and chemical trigger [73]. Consequently, the laser not only causes thermal damage but also sensitizes the tumor to ferroptosis by diminishing antioxidant defenses. These acts are a trigger of ICD, enabling its association with immunotherapy in 18.7% of cases [74,75]. Therefore, the prevalence of stimuli-responsive systems (sensitive to acidic pH and reductive environments) demonstrates the necessity of searching for intratumoral selectivity to minimize systemic toxicity [71].
In contrast, the identification of only one study utilizing selenium (Na2SeO3) points to a critical gap. Since selenium is an essential cofactor in GPX4 activity, its exploration via nanotechnology represents a promising but underutilized therapeutic frontier to overcome metabolic resistance in TNBC [76].

4.4. Biological Mechanisms and the Overcoming of Tumoral Defenses

The analysis of included studies shows that the induction of ferroptosis in TNBC is not only dependent on iron overload, but also on the coordinated disruption of cellular redox homeostasis. The predominance of the Fenton reaction as the principal inductor in 97.9% (n = 47) of works confirms that the targeted generation of hydroxyl (●OH) radicals remains the lead strategy to rupture lipid stability. However, due to the strength of the intrinsic tumor defense systems, most interventions (n = 36; 75%) are concentrated on the inhibition of the GPX4/SLC7A11 axis (System xc-). This blockade is strategic, as it disarms the cystine transport system and GPX4 activity, depriving the cell of its capacity to neutralize lipid peroxides (LPO); thus, cell death becomes inevitable even under moderate iron concentrations [77,78].
The evolution of recent research (n = 8; 16.6%) points to the mapping of escape mechanisms extrinsic to the canonic pathway, introducing alternative targets such as mitochondrial DHODH, the FSP1 system at the plasmatic membrane, and TrxR. The identification of these routes suggests that upon GPX4 blockage, TNBC subpopulations activate mitochondrial defenses to maintain membrane integrity. In this scenario, the development of multifunctional nanosystems that simultaneously attack multiple redox axes, such as utilizing siRNA to silence DHODH or TRIM37, represents a biotechnological trend to reduce recurrence and tumor resistance [54,77,79].
Therefore, the role of ferroptosis in the reversal of MDR, identified in 37.5% (n = 18) of studies, suggests that lipid peroxidation induced by nanosystems promotes a biophysical alteration in the fludity of the cytoplasmic membrane. This destabilizes efflux proteins, such as P-glycoprotein (P-gp), which would normally excrete cytotoxic agents and reduce intracellular ATP levels. This biomechanical and biochemical synergy explains the increased effectiveness of drugs such as doxorubicin, cisplatin, and camptothecin when associated with ferroptosis-inducing platforms [80,81,82].
At last, a change in paradigm was observed with the emergence of ferroptosis as an immunomodulatory mechanism (n = 9; 18.7%). Different from apoptosis, ferroptotic death is basically immunogenic, triggering the release of damage-associated molecular patterns (DAMPs), such as HMGB1 and ATP. Evidence suggests that ferroptosis can remodel the TNBC microenvironment, amplifying the effectiveness of immunotherapies by favoring the recruitment and activation of tumor-infiltrating T-lymphocytes [75,83].

4.5. Study Limitations and Recommendations for Future Research

The limitations identified in this study are primarily related to the exclusion of evidence from in vitro trials and pre-clinical murine models, which hinders the definitive validation of pharmacokinetics, biodistribution, and systemic toxicity in humans. Although fundamental, animal models fail to exactly replicate the heterogeneity of the human immune system and the specific stromal barriers of breast cancer in real patients.
Additionally, the high heterogeneity in the nanotechnological architectures and the absence of standardized synthesis protocols hinder direct comparisons between studies; thus, the analyzed data remains predominantly qualitative. The exclusive focus on iron and selenium also limited the analysis of other metabolic cofactors and the host’s nutritional status, both of which influence the ferroptotic response. A critical imbalance was identified in the exploration of micronutrients, where the role of selenium remains underestimated compared with iron overload, and the restriction to the isolated ferroptosis mechanism hindered the investigation of synergic interactions with other programmed cell death pathways.
Based on these gaps, future research should focus on developing selenium-based nanoplatforms aimed at the enzymatic modulation of GPX4 as an alternative to iron overload and dependence on the Fenton reaction. It is recommended to investigate the crosstalk between ferroptosis and systems such as the Ferroptosis Suppressor Protein 1–Coenzyme Q10 (FSP1-CoQ10) and DHODH to develop multi-target nanotherapies that block metabolic escape routes and prevent tumor recurrence. Finally, performing rigorous pharmacokinetic analyses to document the final fate and the clearance of inorganic platforms in the reticuloendothelial system over extended temporal windows is essential.

5. Conclusions

This scoping review mapped the context of ferroptosis-inducing nanoplatforms in breast cancer, synthesizing the current evidence and identifying the gaps that prevent the clinical translation of these technologies. The results show a growing body of literature that is still highly concentrated in laboratory tests (in vitro) and animal models, indicating that the field is still in a pre-clinical stage.
The mapping revealed that nearly all strategies (97.9%) focus on iron overload and the Fenton reaction. This demonstrates a saturation of research in this axis, whereas the selenium pathway remains strikingly underreported (n = 1). Furthermore, the lack of methodological standardization between different types of nanoparticles is a major barrier to comparing results and establishing safe treatment protocols.
In summary, this review achieves its objective of providing a roadmap of current research trajectories and gaps, indicating that the future of the field depends on expanding to models of higher biological complexity and diversifying nutritional and biochemical targets. The identified gaps serve as a guideline for the design of future primary investigations, directing efforts to areas of low evidence density, such as longitudinal follow-up and clinical phase trials.

Supplementary Materials

The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/sci8060130/s1, Table S1: Full electronic search strategy for PubMed/MEDLINE; Checklist S1.

Author Contributions

For this article, all authors contributed equally to the conception, planning, analysis, and interpretation of data, as well as writing and editing the manuscript. All authors have read and agreed to the published version of the manuscript.

Funding

This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Brazil (CAPES)—Finance Code 001. This research was partially supported by the Brazilian Research Council (CNPq) (CNPq: process 304312/2025-8 and CNPq: process no 313985/2023-5) and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior-Brasil (CAPES)—Finance Code 001.

Data Availability Statement

The data presented in this study are available upon request from the corresponding author.

Acknowledgments

We thank the Graduate Program in Health and Development in the Central-West Region, Medical School, Federal University of Mato Grosso do Sul, Campo Grande, and the Federal University of Mato Grosso do Sul-UFMS for the support. The authors also thank the Coordination for the Improvement of Higher Education Personnel (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior-CAPES).

Conflicts of Interest

The authors declare no conflicts of interest.

Abbreviations

The following abbreviations are used in this manuscript:
ATPAdenosine triphosphate
DAMPsDamage-associated molecular patterns
DHODHDihydroorotate dehydrogenase
FSP1-CoQ10Ferroptosis suppressor protein 1-Coenzyme Q10
GPX4Glutathione peroxidase 4
GSHGlutathione
HMGB1High mobility group box 1
ICDImmunogenic cell death
JBIJoanna Briggs Institute
MDRMultidrug resistance
MOFsMetal–organic frameworks
MPNsMetal–phenolic networks
MRIMagnetic resonance imaging
Na2SeO3Sodium selenite
NIRNear-infrared
●OHHydroxyl radical
PDOsPatient-derived organoids
PDXPatient-derived xenografts
P-gpP-glycoprotein
PUFAsPolyunsaturated fatty acids
PRISMA-ScRPreferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews
PTTPhotothermal therapy
ROSReactive oxygen species
SDTSonodynamic therapy
siRNASmall interfering RNA
SLC7A11Solute carrier family 7 member 11
SPIONsSuperparamagnetic iron oxide nanoparticles
TMETumor microenvironment
TNBCTriple-negative breast cancer
TrxRThioredoxin reductase

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Figure 1. PRISMA-ScR flow diagram of the study selection process.
Figure 1. PRISMA-ScR flow diagram of the study selection process.
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Figure 2. Distribution of the studies included per country of origin (n = 48).
Figure 2. Distribution of the studies included per country of origin (n = 48).
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Figure 3. Distribution of the studies included per year of publication (n = 48).
Figure 3. Distribution of the studies included per year of publication (n = 48).
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Figure 4. Distribution of the included studies per type of experimental design.
Figure 4. Distribution of the included studies per type of experimental design.
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Figure 5. Frequency of the utilization of breast cancer cell lines in the included studies: (a) murine cell lines; (b) human cell lines.
Figure 5. Frequency of the utilization of breast cancer cell lines in the included studies: (a) murine cell lines; (b) human cell lines.
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Table 1. Characteristics of iron-based nanoplatforms for ferroptosis induction in breast cancer: composition, size, and mechanisms of action.
Table 1. Characteristics of iron-based nanoplatforms for ferroptosis induction in breast cancer: composition, size, and mechanisms of action.
No.
[Ref.]		Author (Year)Nanoformulation Platform TypeSize (nm)Mechanism
1
[10]		Zhu et al. (2024)Thermosensitive hydrogel containing gallic acid-modified FeOOH nanospindles and Gallocyanine (Gallo&GFP @FC)Thermosensitive hydrogel (SPION-loaded)156.0Fenton reaction; inhibition of the DKK1/SLC7A11/GPX4 signaling axis.
2
[11]		Pei et al. (2025)Polymeric nanoparticles co-encapsulating iron ions (Fe) and Doxorubicin (SSP-tHB@Fe/DOX)Polymeric nanoparticle110.0Fe(III)-Fe(II) redox cycling; GSH depletion;
chemotherapy (DOX).
3
[12]		Yang et al. (2024)Mesoporous superparamagnetic iron oxide nanoparticles (MSPIONs) loaded with Sorafenib (SFN) and/or Brequinar (BQR) (SFN/BQR@MSPION)Mesoporous SPION (MSPION)70.0Fenton reaction; GPX4 inhibition (via SFN); DHODH inhibition (via BQR).
4
[13]		Zhu et al. (2024)Folic acid (FA)-targeted nanoparticles co-encapsulated with Fe3O4 and Rhein (MP-FA@R-F NPs)Targeted SPION (FA-modified)138.0Fenton reaction; GSH depletion; photothermal therapy (PTT).
5
[14]		Yang et al. (2024)Iron oxide nanoparticles (PEG-Fe3O4) loaded with C5aRA (PEG-Fe3O4@C5aRA)Surface-modified SPION (PEGylated)105.0Fenton reaction;
C5aR1 antagonism; macrophage (TAM) reprogramming.
6
[15]		Ye et al. (2024)Fe3+-doped polydopamine nanoparticles (Fe-PDA) loaded with metformin (Met) (Fe-PDA-Met)Polymeric nanoparticle (PDA-based)193.0Fenton reaction; SLC7A11 inhibition (via MET); Attenuation of T-cell exhaustion.
7
[16]		Han et al. (2024)MIL-101(Fe) metal–organic frameworks containing NaHCO3 (“airbag”), coated with lentinan (LNT) and camouflaged with hybrid membranes (HM/Ef/LNT-MoF)Biomimetic MOF (MIL-101-based)195.4 Fenton reaction; M1 macrophage polarization (via LNT).
8
[17]		Yang et al. (2024)Albumin nanoparticles co-assembled with hemin (iron source), linoleic acid-cystamine (La-Cys), and sulfosuccinimidyl oleate (SSO) (LHS NPs)Protein-based nanoparticle (Albumin)135.2Fenton reaction; inhibition of fatty acid uptake via SSO-mediated CD36 blockade.
9
[18]		Wu et al. (2023)Iron oxide nanoparticles (FeOOH) loaded with siRNA against Prominin2 (Siprom2) and coated with hyaluronic acid (HA) (FeOOH/Siprom2@HA)SPION (FeOOH-based)106.6Fenton reaction; GSH depletion; inhibition of iron efflux.
10
[19]		Gao et al. (2025)Iron-based metal–organic frameworks (Fe-MOF) loaded with Erastin and functionalized with Trastuzumab (Herceptin) (FEH)Antibody-functionalized MOF104.9Fenton reaction; system Xc− inhibition (via Erastin); HER2 blockade.
11
[20]		Abu-Serie et al. (2022)Diethyldithiocarbamate (DDC) nanocomposites with iron oxide nanoparticles (FeO and Fe2O3) via green synthesis (olive leaf extract) (DFeO NPs and DFe2O3 NPs)Green-synthesized SPION53.81/65.13Fenton reaction; ALDH inhibition; GSH depletion.
12
[21]		Wei et al. (2024)Gold–iron oxide (Au-Fe3O4) Janus nanoparticles modified with RGD peptide for tumor-targeting (GION@RGD)Janus nanoparticle (Au-SPION)49.8Fenton reaction; PTT; integrin targeting.
13
[22]		Guo et al. (2025)Mesoporous organosilica nanoparticles (HMONs) containing zero-valent iron (Fe0) camouflaged with DNA fragment-loaded exosomes (Fe@HMON@DNA-Exo)Biomimetic HMON64.9 ± 4.93Fenton reaction; STING pathway activation; GSH depletion.
14
[23]		Du et al. (2021)Core–shell-satellite “nanomaces” composed of a gold (Au) nanorod core, mesoporous silica shell (MSN), and iron oxide nanoparticle (IONP) satellites (Au@MSN@IONP)Au@MSN-based SPION110.0Fenton reaction; NIR hyperthermia; inhibition of iron efflux.
15
[24]		Wang et al. (2025)Copper-doped Prussian Blue (Cu-PB) nanoparticles coated with polydopamine (PDA) delivered via a microneedle patch (Cu-PB@PDA)Cu-doped Prussian Blue-based145.4Fenton reaction; direct GPX4 inhibition (via RSL3); PTT.
16
[25]		Favaron et al. (2023)Organometallic compounds: Ferrocene (Fc) and its oxidized form, the Ferrocenium ion ([Fc]+)Organometallic complexN/A ROS production; lipid peroxidation; mitochondrial dysfunction.
17
[26]		Zhu et al. (2022)Gadolinium (Gd)-doped iron oxide nanoparticles loaded with Dox and functionalized with RGD peptide for targeting (ipGdIO-Dox)Gd-doped SPION (Targeted)110.8Fenton reaction; chemotherapy (Dox); bioimaging.
18
[27]		Xue et al. (2024)Iron-doped hollow silica nanozymes (FeSHS) loaded with Brequinar (BQR) and Lificiguat (YC-1) (FeSHS/BQR/YC-1-PEG)Hollow silica nanozyme156.4Fenton reaction; triple inhibition: GPX4 (via ROS), DHODH (via BQR), and FSP1 (via YC-1).
19
[28]		Li et al. (2021)ZIF-8 metal–organic frameworks loaded with Artemisinin (ART) and coated with Tannic Acid (TA) and ferrous ions (Fe2+) (TA-Fe/ART@ZIF)Core–shell MOF (ZIF-8-based)184.2Fenton reaction; Endoperoxide bridge cleavage (via ART).
20
[29]		Xiang et al. (2025)Bimetallic oxide (Fe/Mo) nanoparticles (FMO@PNPs)Bimetallic nanoamplifier114.3Fenton reaction; Russell mechanism (Mo); A2AR blockade.
21
[30]		He et al. (2020)Liposomes co-encapsulating Ferric Ammonium Citrate (FAC) and a γ-glutamylcysteine synthetase inhibitor (γ-GCSi) (LPOgener)Liposome85.3Fenton-independent LPO induction; GSH depletion.
22
[31]		Zhang et al. (2023)Polyglutamic acid-stabilized Fe3O4 loaded with DHA (Fe3O4-PGA-DHA) and polyaspartic acid-stabilized Fe3O4 loaded with DOX (Fe3O4-PASP-DOX)Polymer-stabilized SPION126.3/103.2Fenton reaction; GPX4 inhibition; DHA activation.
23
[32]		Han et al. (2022)Calcium carbonate (CaCO3) nanoparticles coated with a gallic acid–Fe2+ coordination polymer and loaded with a cisplatin prodrug (Pt(IV)-SA) (PGFCaCO3-PEG)pH-responsive CaCO3 nanoparticle132.8Fenton reaction; chemotherapy; pH modulation.
24
[33]		Zhao et al. (2023)Hinokitiol–iron complex [Fe(hino)3]Organometallic complex (iron ionophore)N/ALabile Iron Pool (LIP) expansion; direct lipid peroxidation.
25
[34]		Zhang et al. (2021)Holo-lactoferrin (hLF)Protein-based nanoplatform (biomolecule)N/AFenton reaction; radiosensitization; HIF-1α inhibition.
26
[35]		Chen et al. (2024)Polydopamine-coated iron oxide nanoparticles (I@P) conjugated to ferritin (FRT) via GSH-responsive disulfide bridges (I@P-ss-FRT)Protein-conjugated SPION123.5Fenton reaction; PTT; GSH depletion.
27
[36] 		Xue et al. (2024)Iron(III)-based metal–organic framework (MOF) assembled with disulfide bridging and loaded with Actinomycin D (ActD) (FessMOF/ActD-PEG)Biodegradable Iron(II)-MOF102.5Fenton reaction; system Xc− inhibition; Ferritinophagy; DNA repair blockade.
28
[37] 		Liu et al. (2025)Ferritin nanocages co-encapsulating ferrous ions (Fe2+) and siRNA (Fe/siGPX4-Fn)Biomimetic Ferritin Nanocage36.5Fenton reaction; GPX4 gene silencing (via siRNA).
29
[38]		Rao et al. (2023)Iron-based metal–organic framework (MIL-101-NH2) loaded with Buthionine Sulfoximine (BSO) and Oxaliplatin (BSO/Oxa@MOF)Iron-based MOF (MIL-101-NH2)148.5Fenton reaction; GPX4 gene silencing (via siRNA).
30
[39] 		Lo et al. (2024)Polymersome nanoreactor containing ferric ions (Fe3+) and glucose oxidase (GOx) (FePSP@GOx)Polymersome Nanoreactor132.3Fenton reaction; starvation therapy (via GOx); GSH depletion.
31
[40] 		Li et al. (2022)Metal–phenolic networks (MPNs) composed of tannic acid (TA) and iron (Fe3+), loaded with a CO prodrug and the photothermal agent IR820 (FeCO-IR820@Fe(III)TA)Metal-Phenolic Network (MPN)162.7Fenton reaction; cytochrome c oxidase inhibition (via CO); PTT.
32
[41] 		Pan et al. (2022)Iron–Porphyrin NMOF (Fe-TCPP) loaded with Tirapazamine (TPZ) and coated with breast cancer cell (BCC) membranes (PFTT@BCCM)Biomimetic NMOF201Fenton reaction; photodynamic therapy (PDT); hypoxia-activated chemotherapy (via TPZ); homologous targeting.
33
[42] 		Wang et al. (2022)Iron-based metal–organic framework (Fe-MIL-101) loaded with glucose oxidase (GOx) (Fe-MIL-101-GOx)Iron-based MOF (Nanozyme)145.4 ± 15.2Fenton reaction; starvation therapy (via GOx); MRI monitoring.
34
[43] 		Zhao et al. (2024)Iron(III)-based coordination polymer (Fe-PVP) loaded with β-lapachone and calcium peroxide (CaO2), modified with Hyaluronic Acid (HA) (HCF@β-lap)Organometallic Compound (Coordination Polymer)237 ± 5.2Fenton cascade reaction; H2O2 self-supply; Ca2+ overload.
35
[44] 		He et al. (2022)Nanohybrids formed by the coordination of a polypeptide (PC-PR), tannic acid (TA), and iron ions (Fe3+) (PCFT)Metal–phenolic network (MPN)158 ± 5Fenton reaction; PTT; GPX4 downregulation.
36
[45] 		Huang et al. (2025)Iron(II)-carbon nanoparticle complex (CNSI-Fe)Carbon-based nanoparticle208.2 ± 5.6Fenton reaction; PTT; lipid peroxidation.
37
[46] 		Cao et al. (2025)ZIF-derived carbon nanomaterial (Fe-SAzyme) modified with Polyethylene glycol–thioacetal–Doxorubicin (PEG-TK-DOX) conjugate (SAzyme-DOX)MOF-derived single-atom nanozyme (MOF)156.4 ± 4.3Multi-enzymatic activity (POD/OXD/CAT-like); Fenton reaction; PTT.
38
[47] 		Liu et al. (2024)Iron-doped mesoporous polydopamine (mPDA) nanoparticles loaded with Sorafenib (SRF) and Triphenylphosphine (TPP) (Fe-mPDA@SRF-TPP)Mesoporous polydopamine manoparticle (NPP)153.8 ± 3.8System Xc− inhibition (via SRF); Fenton reaction; Mitochondrial targeting.
39
[48] 		Luo et al. (2023)Ferrocene (Fc)-containing polymer micelles loaded with Auranofin (Aur) and the pro-ferroptotic lipid PE-AA (Aur/PE-AA@M Fc)Ferrocene-bearing polymeric micelle (NPP)136.0 ± 3.1Pro-ferroptotic lipid supplementation; TrxR inhibition; Fenton reaction.
40
[49] 		Xu et al. (2024)Sodium Selenite (Na2SeO3)Free molecule (Selenium-based)N/AATM signaling; Increase in labile Fe2+; Lipid-ROS (L-ROS) generation.
41
[50] 		Pang et al. (2024)Magnesium–iron layered double hydroxides (Mg-Fe LDHs) loaded with Simvastatin (SIM) (Mg-Fe LDH-SIM)Layered double hydroxide (LDH)138.7 ± 1.5Fenton reaction; GSH depletion; Caspase activation.
42
[51] 		Chen et al. (2023)Layered double hydroxides (LDH) co-loaded with iron oxide nanoparticles (IONs) and a DHODH inhibitor (Leflunomide/siR) (siR/IONs@LDH)Layered double hydroxide (LDH) 126.0 ± 12.3Mitochondrial defense blockade (via DHODH); Fenton reaction.
43
[52] 		Nieto; Vega; Martín del Valle (2021)Iron (Fe3+)-doped polydopamine (PDA) nanoparticles loaded with Doxorubicin (DOX) (PDA-Fe-DOX)Polymetic Nanoparticle (NPP)154.2 ± 28.5Fenton reaction; chemotherapy (Dox); redox defense depletion.
44
[53] 		Cao et al. (2023)Iron-based metal–organic framework (Fe-TCPP MOF/FTM) loaded with a sonosensitizer (Ce6) and a radical initiator (AIPH), coated with cancer cell membranes (FTM@AM)Biomimetic Metal–Organic framework (MOF)181.07Fenton reaction; Sonodynamic therapy (SDT); cytoskeletal targeting (F-actin).
45
[54] 		Tian et al. (2024)Perfluorocarbon (PFC) nanodroplets loaded with anti-TRIM37 siRNA, coated with an Iron (Fe3+)-Tannic Acid (TA) network, and modified with Hyaluronic Acid (HA) (PTFTH)Metal–phenolic network (MPN)196 TRIM37 silencing; GSH depletion; Fenton reaction; PTT.
46
[55] 		Bernkop-Schnürch et al. (2024)Fluorinated iron(III) [salophen] chloride complexesFree molecule (organometallic complex)N/ATransferrin receptor (TfR1) pathway; Fenton reaction; Mitochondrial dysfunction.
47
[56] 		Cai et al. (2023)Folic acid (FA)-modified polydopamine (PDA) nanoparticles co-loaded with Camptothecin (CPT) and Iron (Fe) (CPT/Fe@PDA-FA)Polymeric nanoparticle (NPP)161.4Fenton reaction; Folate receptor targeting; chemotherapy (CPT).
48
[57] 		Yujie et al. (2024)Hyaluronic acid-modified zinc–iron peroxide nanocomposites (Fe-ZnO2(a)HA/FZOH)Peroxide nanocomposite134.7Fenton reaction; Extracellular matrix (ECM) degradation; immunotherapy.
Caption: A2AR: Adenosine A2A Receptor; ActD: Actinomycin D; AIPH: 2,2′-Azobis[2-(2-imidazolin-2-yl)propane]dihydrochloride; ALDH: Aldehyde Dehydrogenase; ART: Artemisinin; ATM: Ataxia-Telangiectasia Mutated; BCCM: Breast Cancer Cell Membrane; BQR: Brequinar; BSO: Buthionine Sul-foximine; CAT: Catalase; Ce6: Chlorin e6; CPT: Camptothecin; DDC: Diethyldithiocarbamate; DHA: Dihydroartemisinin; DHODH: Dihydroorotate Dehydrogenase; DOX: Doxorubicin; ECM: Extra-cellular Matrix; FA: Folic Acid; FAC: Ferric Ammonium Citrate; Fc: Ferrocene; FSP1: Ferroptosis Suppressor Protein 1; GOx: Glucose Oxidase; GPX4: Glutathione Peroxidase 4; GSH: Glutathione; HA: Hyaluronic Acid; HER2: Human Epidermal Growth Factor Receptor 2; HMON: Hollow Mesoporous Organosilica Nanoparticle; IONP: Iron Oxide Nanoparticle; LDH: Layered Double Hydroxide; LIP: Labile Iron Pool; LPO: Lipid Peroxidation; L-ROS: Lipid Reactive Oxygen Species; MOF: Metal–Organic Framework; MPN: Metal-Phenolic Network; mPDA: Mesoporous Polydopamine; MSN: Mesoporous Silica Nanoparticle; MSPION: Mesoporous Superparamagnetic Iron Oxide Nanoparticle; N/A: Not applicable; NIR: Near-Infrared; OXD: Oxidase; PDA: Polydopamine; PDT: Photodynamic Therapy; PFC: Per-fluorocarbon; POD: Peroxidase; PR: Progesterone Receptor; PTT: Photothermal Therapy; RGD: Arginylglycylaspartic acid; SAzyme: Single-Atom Nanozyme; SDT: Sonodynamic Therapy; SFN: Sorafenib; siRNA: Small Interfering RNA; SLC7A11: Solute Carrier Family 7 Member 11; SRF: Sorafenib; STING: Stimulator of Interferon Genes; TAM: Tumor-Associated Macrophage; TA: Tannic Acid; TCPP: Tetrakis(4-carboxyphenyl)porphyrin; TfR1: Transferrin Recep-tor 1; TrxR: Thioredoxin Reductase. Source: Elaborated by the authors (2026).
Table 2. Experimental models used in the included studies: cell lines, animal models, and breast cancer subtypes.
Table 2. Experimental models used in the included studies: cell lines, animal models, and breast cancer subtypes.
No.
[Ref.]		Author (Year)TypeCell LineAnimal ModelBreast Cancer Subtype
1
[10]		Zhu et al. (2024)In vitro
In vivo		4T1/
4T1-derived CSCs 		MurineTNBC
(ER−/PR−/HER2−)
2
[11]		Pei et al. (2025)In vitro
In vivo		4T1 MurineTNBC
(ER−/PR−/HER2−)
3
[12]		Yang et al. (2024)In vitro
In vivo		4T1MurineTNBC
(ER−/PR−/HER2−)
4
[13]		Zhu et al. (2024)In vitro
In vivo		4T1MurineTNBC
(ER−/PR−/HER2−)
5
[14]		Yang et al. (2024)In vitro
In vivo
Human samples		4T1MurineTNBC
(ER−/PR−/HER2−)
Human Breast Cancer Tissue HumanAll subtypes (TMA)
6
[15]		Ye et al. (2024)In vitro
In vivo		4T1MurineTNBC
(ER−/PR−/HER2−)
7
[16]		Han et al. (2024)In vitro
In vivo		4T1 MurineTNBC
(ER−/PR−/HER2−)
8
[17] 		Yang et al. (2024)In vitro
In vivo		4T1 MurineTNBC
(ER−/PR−/HER2−)
9
[18] 		Wu et al. (2023)In vitro
In vivo		BCSCs
(4T1-derived)		MurineTNBC
(ER−/PR−/HER2−)
10
[19]		Gao et al. (2025)In vitro
In vivo		BT474 HumanLuminal B
(ER+/PR+/HER2+)
SKBR3HumanHER2+
(ER−/PR−/HER2+)
11
[20] 		Abu-Serie et al. (2022)In vitro
In vivo		MCF-7HumanLuminal A
(ER+/PR+/HER2−)
MDA-MB-231 (CSCs)HumanTNBC
(ER−/PR−/HER2−)
12
[21]		Wei et al. (2024)In vitro
In vivo		4T1MurineTNBC
(ER−/PR−/HER2−)
13
[22] 		Guo et al. (2025)In vitro
In vivo		4T1 MurineTNBC
(ER−/PR−/HER2−)
14
[23] 		Du et al. (2021)In vitro
In vivo 		4T1MurineTNBC
(ER−/PR−/HER2−)
MDA-MB-231HumanTNBC
(ER−/PR−/HER2−)
15
[24] 		Wang et al. (2025)In vitro
In vivo		4T1 MurineTNBC
(ER−/PR−/HER2−)
16
[25] 		Favaron et al. (2023)In vitroMCF-7HumanLuminal A
(ER+/PR+/HER2−)
17
[26] 		Zhu et al. (2022)In vitro
In vivo		4T1MurineTNBC
(ER−/PR−/HER2−)
18
[27] 		Xue et al. (2024)In vitro
In vivo		4T1/Murine TNBC
(ER−/PR−/HER2−)
MCF-7 HumanLuminal A
(ER+/PR+/HER2−)
19
[28] 		Li et al. (2021)In vitro
In vivo		4T1 MurineTNBC
(ER−/PR−/HER2−)
20
[29] 		Xiang et al. (2025)In vitro
In vivo 		4T1MurineTNBC
(ER−/PR−/HER2−)
21
[30]		He et al. (2020)In vitro
In vivo 		4T1 MurineTNBC
(ER−/PR−/HER2−)
22
[31] 		Zhang et al. (2023)In vitro
In vivo		4T1 MurineTNBC
(ER−/PR−/HER2−)
23
[32] 		Han et al. (2022)In vitro
In vivo		4T1 MurineTNBC
(ER−/PR−/HER2−)
24
[33] 		Zhao et al. (2023)In vitro
In vivo		4T1MurineTNBC
(ER−/PR−/HER2−)
MDA-MB-231HumanTNBC
(ER−/PR−/HER2−)
BT549HumanTNBC
(ER−/PR−/HER2−)
25
[34] 		Zhang et al. (2021)In vitro
In vivo		4T1MurineTNBC
(ER−/PR−/HER2−)
MDA-MB-231HumanTNBC
(ER−/PR−/HER2−)
26
[35]		Chen et al. (2024)In vitro
In vivo		4T1 MurineTNBC
(ER−/PR−/HER2−)
27
[36] 		Xue et al. (2024)In vitro
In vivo		4T1 MurineTNBC
(ER−/PR−/HER2−)
28
[37] 		Liu et al. (2025)In vitro
In vivo 		4T1 MurineTNBC
(ER−/PR−/HER2−)
29
[38]		Rao et al. (2023)In vitro
In vivo 		4T1 MurineTNBC
(ER−/PR−/HER2−)
30
[39] 		Lo et al. (2024)In vitro
In vivo		4T1 MurineTNBC
(ER−/PR−/HER2−)
31
[40] 		Li et al. (2022)In vitro
In vivo		4T1 MurineTNBC
(ER−/PR−/HER2−)
32
[41] 		Pan et al. (2022)In vitro
In vivo		4T1 MurineTNBC
(ER−/PR−/HER2−)
33
[42] 		Wang et al. (2022)In vitro
In vivo		4T1 MurineTNBC
(ER−/PR−/HER2−)
34
[43] 		Zhao et al. (2024)In vitro
In vivo		4T1 MurineTNBC
(ER−/PR−/HER2−)
35
[44] 		He et al. (2022)In vitro
In vivo		4T1 MurineTNBC
(ER−/PR−/HER2−)
36
[45] 		Huang et al. (2025)In vitro
In vivo 		4T1 MurineTNBC
(ER−/PR−/HER2−)
37
[46] 		Cao et al. (2025)In vitro
In vivo 		4T1MurineTNBC
(ER−/PR−/HER2−)
38
[47] 		Liu et al. (2024)In vitro
In vivo		4T1 MurineTNBC
(ER−/PR−/HER2−)
39
[48] 		Luo et al. (2023)In vitro
In vivo		4T1/MurineTNBC
(ER−/PR−/HER2−)
MCF-7HumanLuminal A
(ER+/PR+/HER2−)
40
[49] 		Xu et al. (2024)In vitro
In vivo		MDA-MB-231HumanTNBC
(ER−/PR−/HER2−)
MCF-7HumanLuminal A
(ER+/PR+/HER2−)
41
[50] 		Pang et al. (2024)In vitro
In vivo		MDA-MB-231HumanTNBC
(ER−/PR−/HER2−)
MCF-7HumanLuminal A
(ER+/PR+/HER2−)
42
[51] 		Chen et al. (2023)In vitro
In vivo		4T1 MurineTNBC
(ER−/PR−/HER2−)
43
[52]		Nieto; Vega; Martín del Valle (2021)In vitroMDA-MB-231HumanTNBC
(ER−/PR−/HER2−)
MCF-7HumanLuminal A
(ER+/PR+/HER2−)
44
[53] 		Cao et al. (2023)In vitro
In vivo		4T1MurineTNBC
(ER−/PR−/HER2−)
45
[54] 		Tian et al. (2024)In vitro
In vivo		4T1 MurineTNBC
(ER−/PR−/HER2−)
46
[55] 		Bernkop-Schnürch et al. (2024)In vitroMDA-MB-231HumanTNBC
(ER−/PR−/HER2−)
MCF-7HumanLuminal A
(ER+/PR+/HER2−)
47
[56] 		Cai et al. (2023)In vitro
In vivo		 MDA-MB-231HumanTNBC
(ER−/PR−/HER2−)
MCF-7/ADRHumanLuminal A
(ER+/PR+/HER2−)
48
[57] 		Yujie et al. (2024)In vitro
In vivo		4T1 MurineTNBC
(ER−/PR−/HER2−)
Caption: ER: Estrogen Receptor; HER2: Human Epidermal Growth Factor Receptor 2; PR: Progesterone Receptor; TMA: Tissue Microarray including Luminal A, Luminal B, HER2+, and TNBC samples; TNBC: Triple-Negative Breast Cancer. Status Indicators: (+) positive expression; (−) negative expression. Species: mouse models refer to syngeneic 4T1 grafts in BALB/c mice; human models refer to xenografts in nude mice. Source: Elaborated by the authors (2026).
Table 3. Distribution of nanotechnological platforms per therapeutic strategy (n = 48).
Table 3. Distribution of nanotechnological platforms per therapeutic strategy (n = 48).
Primary Platform
(Group)		Combined
Chemotherapy		Multimodal
Therapy
(PTT/SDT/RT)		ImmunotherapyAdjuvant Gene Therapy/(Post-Surgical)
1. MOFs/Nanozymes5720
2. Iron Oxides/SPIONs4321
3. Polymeric Nanoparticles/Micelles4211
4. Polydopamine (PDA)/MPNs2420
5. Biological Base (Exosomes/Membranes)2110
6. Other Inorganics (LDH, Carbon, Se)1210
Total
(n = 48)		18
(37.5%)		19
(39.6%)		9
(18.7%) 		2
(4.2%)
Caption: MOFs: Metal–organic frameworks; SPIONs: superparamagnetic iron oxide nanoparticles; MPNs: metal–phenolic nets; PTT: photothermic therapy; SDT: sonodynamic therapy; RT: radiotherapy. Source: elaborated by the authors (2026).
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Libório, É.L.F.; Freitas, K.d.C.; Pott, A.; Ferreira, R.d.S.; Inada, A.C.; Hiane, P.A.; Donadon, J.R.; Nascimento, V.A.d.; Guimarães, R.d.C.A. Use of Iron in Modulation of Ferroptosis as Therapeutic Strategy in Breast Cancer: A Scoping Review. Sci 2026, 8, 130. https://doi.org/10.3390/sci8060130

AMA Style

Libório ÉLF, Freitas KdC, Pott A, Ferreira RdS, Inada AC, Hiane PA, Donadon JR, Nascimento VAd, Guimarães RdCA. Use of Iron in Modulation of Ferroptosis as Therapeutic Strategy in Breast Cancer: A Scoping Review. Sci. 2026; 8(6):130. https://doi.org/10.3390/sci8060130

Chicago/Turabian Style

Libório, Érika Leite Ferraz, Karine de Cássia Freitas, Arnildo Pott, Rosângela dos Santos Ferreira, Aline Carla Inada, Priscila Aiko Hiane, Juliana Rodrigues Donadon, Valter Aragão do Nascimento, and Rita de Cássia Avellaneda Guimarães. 2026. "Use of Iron in Modulation of Ferroptosis as Therapeutic Strategy in Breast Cancer: A Scoping Review" Sci 8, no. 6: 130. https://doi.org/10.3390/sci8060130

APA Style

Libório, É. L. F., Freitas, K. d. C., Pott, A., Ferreira, R. d. S., Inada, A. C., Hiane, P. A., Donadon, J. R., Nascimento, V. A. d., & Guimarães, R. d. C. A. (2026). Use of Iron in Modulation of Ferroptosis as Therapeutic Strategy in Breast Cancer: A Scoping Review. Sci, 8(6), 130. https://doi.org/10.3390/sci8060130

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