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Review

Current Developments of Iron Oxide Nanomaterials as MRI Theranostic Agents for Pancreatic Cancer

by
Fong-Yu Cheng
1,
Boguslaw Tomanek
2,3,* and
Barbara Blasiak
3
1
Department of Chemistry, Chinese Culture University, Taipei 11114, Taiwan
2
Division of Medical Physics, Department of Oncology, University of Alberta, 8303 112 St. NW, Edmonton, AB T6G 2T4, Canada
3
The Henryk Niewodniczański Institute of Nuclear Physics Polish Academy of Sciences, Radzikowskiego 152, 31-342 Kraków, Poland
*
Author to whom correspondence should be addressed.
J. Nanotheranostics 2025, 6(3), 22; https://doi.org/10.3390/jnt6030022
Submission received: 29 June 2025 / Revised: 3 August 2025 / Accepted: 5 August 2025 / Published: 7 August 2025
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Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive type of pancreatic cancer. PDAC is difficult to diagnose due to a lack of symptoms in early stages, resulting in a survival rate of less than 10%. Moreover, often cancerous tissues cannot be surgically resected due to their deep abdomen location. Therefore, early detection is the essential strategy enabling effective PDAC treatment. Over the past few years, the development of nanomaterials for Magnetic Resonance Imaging (MRI) has expanded and improved imaging quality and diagnostic accuracy. Nanomaterials can be currently designed, manufactured and synthesized with other structures to provide improved diagnosis and advanced therapy. Although MRI equipped with the innovative nanomaterials became a powerful tool for the diagnosis and treatment of patients with various cancers, the detection of PDAC remains challenging. Nevertheless, recent advancements in PDAC theranostics provided progress in the detection and treatment of this challenging type of cancer. Present research in this area is focused on suitable carriers, eliminating delivery barriers, and the development of efficient anti-cancer drugs. Herein we discuss the current applications of iron oxide nanoparticles to the MRI diagnosis and treatment of pancreatic cancer.

1. Introduction

Pancreatic ductal adenocarcinoma (PDAC) is the major type of pancreatic cancer. PDAC is the fourth leading cause of cancer death in Europe and in the US and the seventh leading cause of cancer-related mortality worldwide [1]. The overall five-year survival rate of PDAC is lower than 10% [1]. This poor survival rate is associated with late diagnosis due to the lack of specific symptoms and the low sensitivity and specificity of clinical imaging in the detection of small pancreatic lesions [2,3]. Therefore, patients with PDAC are usually being diagnosed when cancer cells already metastasized and surgery is inefficient; hence the urgent need for early pancreatic cancer detection [4]. Furthermore, PDAC cells are very difficult to be surgically resected because of their location in the deep abdomen. Due to these impediments, currently PDAC can be surgically removed in only 20% of patients [5]. The only choice remains a combination of chemotherapy with various drugs and radiotherapy, yet it still provides limited survival due to the high resistance to chemo- and radiotherapy of pancreatic cancers, in particular in advanced stages [2,3]. Recent attempts of applying immunotherapy using immune checkpoint blockade have shown promise in treating several cancer types, but PDAC patients showed a poor response to this type of treatment [6]. Carbohydrate antigen 19-9 (CA19-9) is the only clinically applicable biomarker, yet its efficacy is limited due to insufficient sensitivity in the early stages of cancer [7].
Current research shows that the pancreatic tumor microenvironment comprises several barriers preventing the delivery of a sufficient amount of drugs into cancerous cells due to the enriched tumor stromal component (fibroblasts and mesenchymal stromal cells) and disorganized vasculature of pancreatic cancer tissues [8,9,10].
Considering these challenges, new approaches are needed allowing the detection of the tumor at very early stages, ideally before metastasis, that may allow more effective treatment. As stated by Borrebaeck, the early detection of PDAC could allow surgical resection in more patients, improving survival [9].
Nanomaterials (NMs) and nanotechnologies have provided new opportunities and strategies to deliver contrast agents and therapeutics to targeted tumors. In recent years, precise diagnosis and targeted therapy in PDAC patients have become a widespread research field [11,12,13,14,15,16,17]. Of particular interest is the application of NMs as contrast agents in magnetic resonance imaging (MRI), a non-invasive and safe imaging technique, providing targeted molecular imaging. Biomarkers used in MRI, comprising both contrast and therapeutic agents, allow high specificity and sensitivity MRI of cancer. The ideal MRI contrast agent has the proper size, a narrow size distribution, excellent magnetic properties (in particular high relaxivity), low toxicity, and good biodegradability and biocompatibility [18]. The safety and toxicity of materials used in humans are the most concerning factors in their clinical applications.
While gadolinium-based contrast agents have proven to provide good visualization of small lesions, their toxicity brought the need for further research of new contrast agents such as iron oxide nanoparticles to ensure patient safety.
Although there are many contrast agents that can meet the needs of the MRI technique (mostly based on gadolinium), few of them can also ensure safety and low toxicity. Among superparamagnetic materials, iron oxide nanoparticles (IONPs) are well-known and currently used contrast agents in MRI diagnosis. Iron oxide NPs were used for the first time clinically to image liver tumor and metastases [19]. Recently, IONPs became a focus of interest due to their low cytotoxicity, simple synthesis and labelling, biocompatibility and low cost of mass production [20]. IONPs can be divided according to their hydrodynamic diameter. The diameter of magnetic iron oxide NPs is usually smaller than a micrometer. SPIOs (superparamagnetic iron oxide particles) are 50 nm to 250 nm in diameter, while the diameters of ultra-small SPIOs (UPSIOs) range from 20 nm to 50 nm. Very small SPIOs (VSPIOs) are less than 20 nm in diameter [21]. The possibility of applying a high concentration of nanoparticles (NPs) without side effects allows to increase their intracellular concentration in pancreatic cancer cells and tumor environments, enabling improved contrast in MRI diagnosis, disease monitoring, drug delivery and therapeutic response [22,23].
Herein we discuss the recent advancement in the design of nanomaterial-based platforms for PDAC diagnosis using the MRI technique. Our aim was to provide an overview of the current role and recent developments of iron oxide-based NPs as MRI and theranostic agents for pancreatic cancer.
For a visualization of the topic of the current mini-review, an example of the application of iron oxide for the enhanced detection of PDAC in the animal model is provided in Figure 1 [14]. The authors constructed ENO1-targeted superparamagnetic (SPIO) nanoparticles (diameter 5–10 nm) for improved pancreatic cancer detection with T2-weighted MRI.

2. Iron Oxide Nanoparticles (NPs) as Theranostic Agents for MR Imaging (MRI) and Pancreatic Ductal Carcinoma (PDAC) Treatment

Unique properties of IONPs triggered their theranostics applications to various types of cancer, including glioblastoma [23], melanoma [24], colon cancer [25], breast cancer [26], central nervous system lymphoma [27] and bone metastasis [28].
SPIONs can be synthesized with drugs to kill tumor cells using gene therapy. For example, cancer-targeted therapies have been developed to block specific cancer genes in hepatocellular carcinoma [29,30]. In particular, Zhang et al. [31] synthesized iRNA modified pluronic P123-PEI for targeted delivery, improving the docetaxel (DTX) therapeutic outcome in PDAC therapy. Wang et al. [32] used SPIO coated with chitosan-PEG grafted polyethyleneimine (CS-PEI) for the delivery of targeted siRNA to orthotopic hepatocellular carcinoma xenografts.
Agents comprising superparamagnetic nanoparticles have been used for both cancer diagnosis and treatment [33] in animal models [32] and in clinical trials [30]. Philip et al. [34] used abraxane® (paclitaxel bound to albumin) as a chemotherapy drug, showing less side effects than other forms of paclitaxel, to treat locally advanced pancreatic cancer (LAPACT). Abraxane® was also used for the treatment of other cancers, such a breast cancer [35] and lung cancer [36].
A new generation of SPIOs enables applications of various diagnostic techniques and therapeutic capabilities in a single formulation [37,38,39]. A schematic illustration of a multifunctional theranostic SPIO is shown in Figure 1. The polymer coating of the SPIO can be loaded with therapeutic agents to facilitate MRI-guided drug delivery, gene delivery, photothermal therapy (PTT), photodynamic therapy (PDT) or magnetic hyperthermia. Cancer specificity can be further increased by using specific proteins and polymers for controlled drug release in response to external stimuli, such as pH, temperature or tumor enzymes [40]. Currently, liposomes, micelles, polymers and IONPs can be modified or loaded with therapeutic and MR imaging agents. Furthermore, high-Z elements such as gold can be utilized in CT imaging [33,40].
Theranostic complexes must be capable of passing through biological barriers, be stable and allow selective delivery to the specific sites [41]. Currently, they can be applied to enable diagnosis with numerous diagnostic modalities, such as MRI or fluorescent labelling [42] as well as to allow various treatment approaches (Figure 2).
Standard, non-targeted NPs accumulate passively in tumors due to their increased blood supply and the enhanced permeability and retention (EPR) effect [43]. Enriching the magnetic surface of the NPs with specific ligands allows increasing selectivity and specificity of NPs (Figure 3). It also reduces side effects of the drug thanks to its selective release in the tumor environment [43].
The EPR efficiency of NPs depends on their composition, size, shape and surface charge. The EPR effect is observed in most cancers, and thus NPs can effectively treat cancers even without specific targeting. However, the EPR effect is limited in PDAC because of the collapse of blood vessels and the presence of a dense desmoplastic stroma [44]. Several nanomedicine-based strategies have been proposed to overcome these problems and their comprehensive description is provided in review papers, for example [45,46]. Selected approaches are provided below.
The PDAC stromal treatment includes the application of enzymes, pharmacological suppression, tumor vasculature modification, stromal targeting peptides, etc. [46]. These approaches include the application of stromal-directed agents that obliterate the dense stromal microenvironment and improve drug delivery [47]. In particular, PEGylated hyaluronidase (PEGPH20) showed a degradation of hyaluronan, reducing PDAC tumor stroma [46]. Another approach is the reduction of the stromal volume, using the FDA-approved drug Abraxane® [48], liposomal irinotecan (nal-IRI) plus 5-fluorouracil and leucovorin (5-FU/LV) [49] and nanoliposomal encapsulated irinotecan (nal-IRI) [50]. Other researchers applied vascular modification to improve drug delivery using, for example, targeting the TGF-β pathway [51] or monoclonal antibodies that showed enhanced vascular access and nanocarriers’ access to the PDAC tumor site [52].
Another approach is to apply stromal targeting therapy. For example, it was shown that cyclical iRGD peptides can increase PDAC vascular access via a nutrient supply pathway [53]. An interesting and promising approach was proposed by Couvreur et al. [54], who applied hexagonal supramolecular nanostructures formed by the squalenoylation of an anticancer nucleoside analogue. They found that these nanoassemblies exhibit strong anticancer activity, following intravenous administration. Wang et al. proposed a photothermal therapy guided with MRI for pancreatic cancer [55]. They used amorphous iron oxide nanoparticles synthesized with a photothermal indocyanine green agent and immunoadjuvant imiquimod. This theranostic agent can be used as a contrast agent for MRI, enabling precise photothermal targeting. Furthermore, MRI can be used to monitor the temperature of tumors and surrounding tissues during treatment, as relaxation times are temperature-dependent. In addition, a properly selected size of nanoparticles may allow penetration of the dense stroma in PDAC. Other authors radiolabeled iron oxide nanoparticles used for MRI with 68Ga and 177Lu as well as 64Cu for positron emission tomography for diagnosis (MRI, PET) and cancer therapy (radionuclides) [56,57,58]. Wang et al. used Enolase 1 targeted iron oxide nanoparticles that can increase the MRI efficiency for detecting PDAC and facilitate the early and accurate detection of PDAC, and that could be combined with drugs for cancer therapy [14]. These NPs can be further synthesized, for example with growth factor 1 (IGF1) for targeted delivery and doxorubicin for treatment [11].
Recently, high-accumulation, active-targeting, efficient drug load became reality for the effective diagnosis and treatment of PDAC using iron oxide poly(lactide-co-glycolide) NPs. These NPs have been shown to increase the local drug concentration at the tumor site and to provide a higher therapeutic efficiency than commonly used NPs. Furthermore, the side effects of anti-cancer drugs are reduced when used with the NPs due to a reduction in non-specific interactions and the enhancement of specific tissue targeting. It was also shown that SPIO can protect payloads from degradative agents and enhance the biological stability of the therapeutic agent [59,60].
To achieve active targeting and precise diagnosis, nanomaterials’ surfaces are required to be conjugated with specific ligands such as antibody, aptamer, protein, DNA, peptide or other biomolecules to actively recognize cancer cells. Figure 4 shows the strategies used for the application of biomolecule-modified NPs to target and MR-image PDAC using specific biomarkers. In previous reports, plectin-1 [61], carbohydrate antigen-19-9 (CA19.9) [62], urokinase plasminogen activator [63], claudin-4 [64], insulin-like growth factor-1 receptor (IGF-1R) [65], galectin-1 [66], integrin αvβ6 [67], integrin αvβ3 [68] and surviving [69] have been investigated in pancreatic cancer diagnosis using various imaging techniques. Plectin-1 is present in the membrane of both murine and human PDAC cells; 93% of PDAC patients are plectin-1 positive, and the specificity and sensitivity of plectin-1 in distinguishing malignant from benign lesions are close to 83~84% [36,45]. When specific ligand-conjugated NPs successfully target the cancer cells, drugs carried by NPs can also be released and accumulate in cancer cells and kill them. Compared to the passive accumulation of NPs (EPR effect), the diagnosis and therapeutic efficiencies of active targeting and accumulation are superior.
Until now, various NPs and nanocomposites have been developed and showed a great potential to treat PDAC. However, the suitable NPs for PDAC treatment are limited in clinical applications considering the requirements and safety. The ideal theranostic (diagnosis and treatment) agents are required to have low cytotoxicity, excellent biodegradation and biocompatibility, as well as good stability in saline. Among the NPs, only gold and iron oxide nanoparticles were approved by the FDA to use in humans but only iron oxide NPs could be used as an MRI contrast agent due to their low toxicity and the magnetic properties required for an MRI contrast agent [70,71,72]. Among NPs, iron oxide NPs have received attention in MRI-related cancer theranostics. Magnetite (Fe3O4) NPs are the most commonly used iron oxide NPs for MRI because they exhibit very strong T2 shortening and thus image contrasting properties. Fe3O4-based NPs have also been applied to various other biomedicial applications [22,70].
Several types of magnetic iron oxide-based contrasts have been approved by the food and drug administration (FDA) in 1996 for the detection of liver lesions and commercialized (Table 1 [71]. The most popular is the contrast agent AMI-25 (ferumoxides (Feridex® in the USA, Endorem® in Europe) with a particle size of 120 to 180 nm, and ferucarbotran (Resovist®) with a particle size of about 60 nm. They consist of dextran-coated iron oxide. The details of clinically used IONPs are provided by Wang et al. [72]. However, currently, Feridex® is not commercially available [73]. Resovist® is current available in only a few countries. Other iron oxide-based contrast agents have been stopped for further development or withdrawn from the market. The SPIO agent Ferumoxytol (Feraheme®) is approved for the treatment of iron deficiency in adult chronic kidney disease patients. Ferumoxytol, comprising iron oxide NPs surrounded by carbohydrates, is being explored as a potential imaging approach for evaluating lymph nodes and certain liver tumors [71,73,74].
Table 1. Applications of magnetic Fe3O4 NPs in clinical settings ([71]—open access).
Table 1. Applications of magnetic Fe3O4 NPs in clinical settings ([71]—open access).
NameShort NameSize (nm)CoatingBlood Half Life in Patientr1
(mmol−1s−1)		r2
(mmol−1s−1)		Type of ContrastClinical DoseApplication
FerumoxideAMI-258120–180Dextran10 min24100–160Negative30 μmol Fe/kgLiver/spleen imaging
FerumoxytolAMI-72283Carboxymethyl-dextran14 h1589Positive50–400 μmol Fe/kgAngiography IV
FerumoxsilAMI-121300SilicaNot available372Negative105 mg/patientGI oral imaging
FerumoxtranAMI-22730Dextran24–30 h2244–85Positive /Negative45 μmol Fe/kgLymph node bone imaging
FerugloseNC1011 5010–20Carboxydrate polyethylene glycol2 h2035Positive36 μmol Fe/kgPerfusion angiography
Ferucarbotran SHU-555ASHU-555A60–80Carboxydextran12 min25164–177Negative8-12 μmol Fe/kgLiver/spleen IV imaging
Ferucarbotran SHU-555CSHU-555C20–50Carboxydextran6–8 h757Positive40 μmol Fe/kgPerfusion lymph node bone marrow IV
Despite the commercial challenges of SPIOs, multiple in vivo and in vitro studies have shown much lower iron oxide toxicity when compared to other contrast agents, such a gadolinium [74,75,76]. However, it was shown that iron oxide NPs generated the reactive radical OH*. Wang et al. [73] reported that iron oxide NPs with a diameter below 5 nm showed some toxicity to several organs at a dosage of iron oxide NPs exceeding 100 mg/kg [34,60,74,77,78]. No apparent toxicity was observed when the size of iron oxide NPs was larger than 5 nm. Notably, iron oxide NPs are used in vivo in much lower doses than 100 mg/kg. Furthermore, the toxicity of iron oxide NPs depends on various factors, including the synthesis method, surface area, particle size, surface coating composition and charge [79,80,81]. Toxicity could be further reduced by a surface modification [82]. Furthermore, capping agents are frequently used on iron oxide NPs’ surface to avoid aggregation and provide stability as well as reduce toxicity. Overall, iron oxide NPs are considered a safe nanomaterial for in vivo and in vitro studies.
Jnt 06 00022 g004
Figure 4. Scheme of the use of biomarker-modified NPs to target and image PDAC. The references are provided in Table 2.
Figure 4. Scheme of the use of biomarker-modified NPs to target and image PDAC. The references are provided in Table 2.
Jnt 06 00022 g004
Table 2 shows the recently developed iron-based MRI contrast agents for the diagnosis of pancreatic cancer.
Table 2. Iron-based MRI theranostics for pancreatic cancer (MFN: magnetofluorescent nanoparticles; SPIO: superparamagnetic iron oxide; IONP: iron oxide nanoparticle; USPIO: ultra-small superparamagnetic iron oxide).
Table 2. Iron-based MRI theranostics for pancreatic cancer (MFN: magnetofluorescent nanoparticles; SPIO: superparamagnetic iron oxide; IONP: iron oxide nanoparticle; USPIO: ultra-small superparamagnetic iron oxide).
Type of NPsHydrodynamic Size
(or Core Size)		Biomarker on NPsStatus and Relevant FindingsReference
MFN~39 nmPlectin-1 targeted peptides (PTP)About 3.13% of injected dose of MFN presented in the tumors. The MRI sensitivity was 20-fold higher than the detection threshold.[61]
SPION29 nm
(SPION: 9–15 nm)		Plectin-1 antibodyThe accumulation amount of the plectin-1 antibody conjugated SPION was ~10 times greater than that of bare SPION in tumor tissue.[15]
IONP41 nmBombesin (BN) peptideThe cellular uptake amount of BN-IONPs was ~1.5 times greater than that of IONPs in BxPC-3 cells.[83]
USPIO96 nmpancreatic cancer targeting peptide (CKAAKN)CKAAKN-USPIO could specifically and highly internalize into CKAAKN-positive BxPC-3 cells. The CKAAKN-USPIO uptake efficiency of positive BxPC-3 cells is ~1.2 times larger than that of negative BxPC-3 cells.[12]
IONP24 nm
(IONP: 10 nm)		triple single chain antibodies (triple scAbs)The cellular uptake (Fe amount) of IONPs-PEG-MCC triple scAbs and IONPs were separately ~1.0 pg/cell and ~0.2 pg/cell.[84]
Fe3O4 NPs27 nm
(Fe3O4 core: 9.9 nm)		Emodin (EMO)The cumulative EMO amount of EMO-Fe3O4 NPs is ~1.5 times larger than that of EMO alone in BxPC-3 cells.[13]
SPION30 nm
(SPION: 5–10 nm)		Enolase 1 (ENO1)ENO1-SPIO nanoparticles using the ENO1 antibody can increase the efficiency of detection of PDAC by in vitro and in vivo MRI (the r1/r2 values of SPIO and ENO1-SPIO were 2.7 and 3.0 in CFPAC-1 cells, respectively)[14]
SPIOSPIO: 10 nmUrokinase plasminogen activator
receptor (uPAR)		The targeting efficiency of Cy5.5-uPAR-SPIOs was 3- to 4-fold higher than that of the mice that received free Cy5.5-peptides.[63]
IONP65.9 nm
(IONP: 22 nm)		uPAR1. uPAR-IONP-Gem showed approximately 50% tumor growth inhibition, which was significantly different from the free Gem and non-targeted IONP-Gem groups.
2. This work found that there was a 4.8-fold signal decrease in the tumors of mice treated with targeted ATF-IONP-Gem compared to the tumors of mice that received non-targeted IONPs.		[85]
IONP107 nm
(IONP: 12 nm)		anti-CD47 antibody1. This work demonstrated that functionalizing the anti-CD47-IONPs greatly improves their cellular uptake by pancreatic cancer cells.
2. The anti-CD47-IONPs and anti-CD47 antibody promoted apoptosis the induction of Panc354 cells were separately ~2.1 and 1.1 (fold change to control).		[78]
IONP17 nm
(IONP: 10 nm)		human insulin-like growth factor1
(IGF1)		1. The signal intensities of the tumor area in the mice that received IGF1-IONPs were 996 and 1301, as compared to 319 and 371 in the mice that received BSA-IONPs.
2. The ex vivo images of tumors and normal organs showed the presence of high levels of optical signal in tumors injected with IGF1-IONPs (signal intensity: 898) but not BSA-IONPs (signal intensity: 398).		[11]
Kelly et al. synthesized plectin-1 targeted peptides (PTP)-conjugated magnetofluorescent NPs to create an MRI contrast agent to detect PDAC in mouse models [61]. This study showed about 3.13% of the injected dose of nanomaterial to be present in the tumors, and the MRI sensitivity to be 20-fold higher than the detection threshold. Similar results were also shown in Chen’s study [15], where SPIONs were conjugated with plectin-1 antibody to create a multi-functional targeted nanoparticle (Plectin-SPION). MR images showed that the Plectin-SPION accumulated mostly in MIAPaCa2 and XPA-1 carcinoma cells but not in non-carcinoma MIN6 cells.
Montet et al. developed a bombesin (BN) peptide–nanoparticle conjugate (BN-CLIO) to distinguish between a normal pancreas and PDAC [83]. The authors used a model and showed that BN-CLIO accumulation in the pancreas was depended on the receptor presence. BN-CLIO decreased the T2 relaxation time of the tumor, improving MRI diagnosis in a pancreatic cancer model.
Zhu et al. developed targeting peptide (CKAAKN)-functionalized polymeric magnetic nanoparticles to improve the pancreatic tumor-targeting delivery and MRI contrast. CKAAKN can specifically bind to pancreatic cancer cell membrane receptors via Wnt protein-mediated endocytosis, hence providing a more effective diagnostic accuracy of pancreatic cancer [12]. Similar results were observed in IONPs-PEG-scAbMUC4-scAbCEACAM6-scFvCD44v6 (IONPs-PEG-MCC triple scAbs) nanocomposites [84]. MUC4, CEACAM6 and CD44v6 are potential biomarkers for targeting PDAC. The transverse relaxivity (R2 = 1/T2) of IONPs-PEG-MCC triple scAbs is 104.2 mM−1s−1 at 3.0 T. The cell uptake efficiency of IONPs-PEG-MCC triple scAbs is five times higher than the standard IONPs-PEG. The main reason of this very high uptake is that triple scAbs can specifically target pancreas cancer cells. Ren et al. [13] developed emodin (EMO)-loaded, Cy7-functionalized, PEG-coated Fe3O4 (Fe3O4-PEG-Cy7-EMO) for MRI of pancreatic cancer. EMO has been reported to sensitize human pancreatic cancer cells to EGFR inhibitor through suppressing the Stat3 signaling pathway [14]. Wang et al. [85] developed ENO1-targeted superparamagnetic iron oxide nanoparticles for detecting pancreatic cancer. ENO1 overexpression could be found in pancreatic cancer patients and ENO1 located on cell membranes [86]. Yang et al. [63] reported that urokinase-type plasminogen activator receptor (uPAR)-targeted SPIO accumulated specifically within the tumor of an orthotopic human pancreatic cancer xenograft model in nude mice.
It has also been shown that over 86% of pancreatic cancer tissues have high levels of uPAR expression in tumor cells, endothelial cells, and stromal fibroblasts and macrophages [87]. In similar studies, Lee et al. [88] used the uPAR-targeted nanocomposites (ATF-IONP-Gem) constructed by conjugating IONPs with the ATF peptide of the receptor-binding domain of uPA. ATF-IONP-Gem provided contrast enhancement in the MRI of pancreatic cancer following the receptor-mediated endocytosis of ATF-IONP-Gem into cancer cells. Zhang et al. [17] developed a nanocomposite (PCN-Fe(III)-PTX NPs) composed of an Fe(III)-complexed porous coordination network (PCN) and PTX to treat pancreatic cancer. PCN-Fe(III)-PTX NPs were found to be suitable for use as a T1 contrast agent and to be viable in monitoring therapeutic efficacy. Besides the above biomarkers, an anti-phagocytosis signal, the CD47 receptor, has also been found to have meaningful expression in pancreatic cancer cells. The CD47 receptor was observed on pancreatic cancer cells, but not on normal pancreas cells. Trabulo et al. [78] developed anti-CD47 antibody-modified iron oxide magnetic NPs for treating pancreatic cancer. They observed their in vitro effectiveness following administration in CD47-positive pancreatic cancer cells. Zhou et al. [11] studied IONPs conjugated to human insulin-like growth factor1 (IGF1) that selectively bind to IGF1-receptors in pancreatic cancer cells. IGF1-IONPs showed efficient tumor penetration in an orthotopic human-derived tumor model.

3. Conclusions and Future Directions

Currently, early detection is an important key point in decreasing the mortality rate of pancreatic cancers, including PDAC. The tumor-accumulation and targeting ability of NPs could enhance PDAC detection at early stages, considerably improving survival and clearly showing the region of surgical resection. However, the stromal barriers of PDAC may reduce the deeper penetration and intratumoral distribution of NPs. To overcome this problem, many specific ligands have been applied on the surface of NPs, increasing their penetration into PDAC cells. Nevertheless, the accumulated amount of NPs in the PDAC region is still very limited. In other words, the increase in the accumulation of NPs in PDAC still can and should be improved. Compared to the detection of the early stage of PDAC, inefficient detection still hinders treatment and surgical resection, particularly in late cancer stages in patient with PDAC. Therefore, NPs carrying drugs combined with chemotherapy or/and radiotherapy may provide improvement to the treatment of PDAC at any stage. While using NPs in cancer therapy is very promising, nano-toxicity requires attention, especially when using new NPs.
MRI offers an increasingly reliable visualization of pancreatic cancers and provides information about staging and monitoring treatment response. Recently, a hybrid imaging technology, combining positron emission tomography (PET) and MRI (PET/MRI), has received increased attention. Simultaneous PET and MRI is a unique clinical tool providing diagnostic improvement in comparison with using each technique alone. MRI anatomical data combined with PET sensitivity provides an additional, new diagnostic tool for the early detection and specific diagnosis of PDAC. As pancreatic cancer is difficult to assess and treat due to its nature and the anatomic location of the pancreas, PET sensitivity may provide a suitable tool for pancreatic cancer detection, staging, surgical planning and treatment monitoring [58].
Overall, iron oxide-based NPs have been developed to overcome detection and therapeutic limitations in cancer identification, and the development of active NPs represents an exciting opportunity to improve pancreatic cancer diagnoses and outcomes.

Author Contributions

F.-Y.C., B.T. and B.B. were responsible for reviewing the literature and preparing the manuscript. F.-Y.C.: Conceptualization, writing—review and editing, writing—original draft preparation, visualization; B.T.: Conceptualization validation, writing—review and editing, funding acquisition, B.B.: Conceptualization validation, writing—review and editing. All authors have read and agreed to the published version of the manuscript.

Funding

This study was partially financed by the National Science Centre (Poland) (project Harmonia 2018/30/M/NZ5/00844).

Conflicts of Interest

The authors declare no conflicts of interest.

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Figure 1. Detection of pancreatic tumor by in vivo MRI of ENO1-targeted superparamagnetic iron oxide nanoparticles (SPIOs) modified with a dextran-graft-polycaprolactone (Dex-g-PCL) polymer (ENO1-Dex-g-PCL/SPIO). (A) MRI of ENO1-Dex-g-PCL/SPIO nanoparticles in a pancreatic cancer xenograft model. (B) Compared with PBS control group and SPIO group, the T2 signal intensity of tumor tissue significantly decreased, and the tumor gradually darkened over time, in which the peak of enhancement was at 24 h in ENO1-SPIO group. (C) IHC staining (40×) of the pancreatic tumor tissues 24 h after injection with ENO1-SPIO nanoparticles. (D) Prussian blue staining (40×) of the pancreatic tumor tissues 24 h after injection with ENO1-SPIO or SPIO. More positive iron particles were found in ENO1-SPIO group. Results were achieved from representative experiments in triplicate and were shown as mean ± standard deviation (SD) ([14]—open access).
Figure 1. Detection of pancreatic tumor by in vivo MRI of ENO1-targeted superparamagnetic iron oxide nanoparticles (SPIOs) modified with a dextran-graft-polycaprolactone (Dex-g-PCL) polymer (ENO1-Dex-g-PCL/SPIO). (A) MRI of ENO1-Dex-g-PCL/SPIO nanoparticles in a pancreatic cancer xenograft model. (B) Compared with PBS control group and SPIO group, the T2 signal intensity of tumor tissue significantly decreased, and the tumor gradually darkened over time, in which the peak of enhancement was at 24 h in ENO1-SPIO group. (C) IHC staining (40×) of the pancreatic tumor tissues 24 h after injection with ENO1-SPIO nanoparticles. (D) Prussian blue staining (40×) of the pancreatic tumor tissues 24 h after injection with ENO1-SPIO or SPIO. More positive iron particles were found in ENO1-SPIO group. Results were achieved from representative experiments in triplicate and were shown as mean ± standard deviation (SD) ([14]—open access).
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Figure 2. Applications of IONPs for cancer diagnosis and treatment.
Figure 2. Applications of IONPs for cancer diagnosis and treatment.
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Figure 3. Schematic representation of the enhanced permeability (EPR) and retention effect.
Figure 3. Schematic representation of the enhanced permeability (EPR) and retention effect.
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Cheng, F.-Y.; Tomanek, B.; Blasiak, B. Current Developments of Iron Oxide Nanomaterials as MRI Theranostic Agents for Pancreatic Cancer. J. Nanotheranostics 2025, 6, 22. https://doi.org/10.3390/jnt6030022

AMA Style

Cheng F-Y, Tomanek B, Blasiak B. Current Developments of Iron Oxide Nanomaterials as MRI Theranostic Agents for Pancreatic Cancer. Journal of Nanotheranostics. 2025; 6(3):22. https://doi.org/10.3390/jnt6030022

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Cheng, Fong-Yu, Boguslaw Tomanek, and Barbara Blasiak. 2025. "Current Developments of Iron Oxide Nanomaterials as MRI Theranostic Agents for Pancreatic Cancer" Journal of Nanotheranostics 6, no. 3: 22. https://doi.org/10.3390/jnt6030022

APA Style

Cheng, F.-Y., Tomanek, B., & Blasiak, B. (2025). Current Developments of Iron Oxide Nanomaterials as MRI Theranostic Agents for Pancreatic Cancer. Journal of Nanotheranostics, 6(3), 22. https://doi.org/10.3390/jnt6030022

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